Trial Outcomes & Findings for Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (NCT NCT03037385)

NCT ID: NCT03037385

Last Updated: 2025-05-31

Results Overview

MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 590 participants
• Primary outcome timeframe: Up to approximately 30.8 months
• Results posted on: 2025-05-31

Participant Flow

A total of 590 participants with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET mutation-positive medullary thyroid cancer (also known as RET-mutant MTC), RET fusion-positive thyroid cancer (TC) and other advanced solid tumors took part in the study at 74 investigative sites across 13 countries from 17 March 2017 to 21 March 2024. The study was divided into two parts: Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion).

For Phase I, The number of participants in each arm within the participant flow reflects the arms they were originally assigned to, whereas numbers reported in the pharmacokinetics outcome measure (OM) represent the number based on actual treatment received by the participants. 1 participant assigned to the 200/100 mg arm received the 100/100 mg treatment. Hence, was counted under the 100/100 mg arm in the PK-evaluable population.

Participant milestones

Measure	Phase I: Pralsetinib 30 mg Participants received pralsetinib 30 milligrams (mg), orally, once a day (QD) until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 60 mg Participants received pralsetinib 60 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100 mg Participants received pralsetinib 100 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200 mg Participants received pralsetinib 200 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 300 mg Participants received pralsetinib 300 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 400 mg Participants received pralsetinib 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 600 mg Participants received pralsetinib 600 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100/100 mg Participants received pralsetinib 100 mg, orally, twice a day (BID) until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200/100 mg Participants received pralsetinib 200 mg in the morning and then 100 mg in the evening orally until discontinuation due to toxicity, disease progression, or other reasons.	Phase II: Pralsetinib 400 mg Participants with advanced NSCLC, advanced non-resectable TC and other advanced non-resectable solid tumors with various rearranged during transfection (RET)-alterations were enrolled in this arm to receive pralsetinib, 400 mg, QD until discontinuation due to toxicity, disease progression, or other reasons.
Overall Study STARTED	2	6	5	13	11	12	4	5	4	528
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	2	6	5	13	11	12	4	5	4	528

Reasons for withdrawal

Measure	Phase I: Pralsetinib 30 mg Participants received pralsetinib 30 milligrams (mg), orally, once a day (QD) until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 60 mg Participants received pralsetinib 60 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100 mg Participants received pralsetinib 100 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200 mg Participants received pralsetinib 200 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 300 mg Participants received pralsetinib 300 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 400 mg Participants received pralsetinib 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 600 mg Participants received pralsetinib 600 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100/100 mg Participants received pralsetinib 100 mg, orally, twice a day (BID) until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200/100 mg Participants received pralsetinib 200 mg in the morning and then 100 mg in the evening orally until discontinuation due to toxicity, disease progression, or other reasons.	Phase II: Pralsetinib 400 mg Participants with advanced NSCLC, advanced non-resectable TC and other advanced non-resectable solid tumors with various rearranged during transfection (RET)-alterations were enrolled in this arm to receive pralsetinib, 400 mg, QD until discontinuation due to toxicity, disease progression, or other reasons.
Overall Study Adverse Event	0	0	1	0	0	0	0	0	0	6
Overall Study Death	1	4	2	2	5	2	1	4	3	240
Overall Study Initiation of Another Therapy	1	0	0	0	0	0	0	1	0	2
Overall Study Lost to Follow-up	0	0	0	0	0	1	0	0	0	16
Overall Study Physician Decision	0	0	0	0	0	0	0	0	0	1
Overall Study Progressive Disease	0	1	1	5	2	0	1	0	0	30
Overall Study Withdrawal by Subject	0	0	1	2	1	3	0	0	0	52
Overall Study Reason Not Specified	0	1	0	4	3	6	2	0	1	181

Baseline Characteristics

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Phase I: Pralsetinib 30 mg n=2 Participants Participants received pralsetinib 30 milligrams (mg) orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 60 mg n=6 Participants Participants received pralsetinib 60 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100 mg n=5 Participants Participants received pralsetinib 100 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200 mg n=13 Participants Participants received pralsetinib 200 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 300 mg n=11 Participants Participants received pralsetinib 300 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 400 mg n=12 Participants Participants received pralsetinib 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 600 mg n=4 Participants Participants received pralsetinib 600 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 100/100 mg n=5 Participants Participants received pralsetinib 100 mg, orally, twice a day (BID) until discontinuation due to toxicity, disease progression, or other reasons.	Phase I: Pralsetinib 200/100 mg n=4 Participants Participants received pralsetinib 200 mg in the morning and then 100 mg in the evening orally until discontinuation due to toxicity, disease progression, or other reasons.	Phase II: Pralsetinib 400 mg n=528 Participants Participants with advanced NSCLC, advanced non-resectable TC and other advanced non-resectable solid tumors with various rearranged during transfection (RET)-alterations were enrolled in this arm to receive pralsetinib, 400 mg, QD until discontinuation due to toxicity, disease progression, or other reasons.	Total n=590 Participants Total of all reporting groups
Age, Continuous	54.5 years STANDARD_DEVIATION 9.2 • n=5 Participants	49.5 years STANDARD_DEVIATION 18.0 • n=7 Participants	51.2 years STANDARD_DEVIATION 13.2 • n=5 Participants	53.8 years STANDARD_DEVIATION 13.6 • n=4 Participants	60.6 years STANDARD_DEVIATION 11.0 • n=21 Participants	49.2 years STANDARD_DEVIATION 17.8 • n=8 Participants	59.5 years STANDARD_DEVIATION 9.1 • n=8 Participants	63.0 years STANDARD_DEVIATION 11.09 • n=24 Participants	61.8 years STANDARD_DEVIATION 18.25 • n=42 Participants	57.7 years STANDARD_DEVIATION 12.6 • n=42 Participants	57.5 years STANDARD_DEVIATION 12.8 • n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	4 Participants n=21 Participants	3 Participants n=8 Participants	3 Participants n=8 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants	257 Participants n=42 Participants	283 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	9 Participants n=8 Participants	1 Participants n=8 Participants	4 Participants n=24 Participants	2 Participants n=42 Participants	271 Participants n=42 Participants	307 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	19 Participants n=42 Participants	28 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants	11 Participants n=21 Participants	9 Participants n=8 Participants	4 Participants n=8 Participants	3 Participants n=24 Participants	4 Participants n=42 Participants	465 Participants n=42 Participants	516 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants	0 Participants n=42 Participants	44 Participants n=42 Participants	46 Participants n=42 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	203 Participants n=42 Participants	209 Participants n=42 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants	2 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants	6 Participants n=42 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants	11 Participants n=21 Participants	9 Participants n=8 Participants	4 Participants n=8 Participants	3 Participants n=24 Participants	4 Participants n=42 Participants	284 Participants n=42 Participants	331 Participants n=42 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	32 Participants n=42 Participants	39 Participants n=42 Participants

PRIMARY outcome

Timeframe: Up to approximately 30.8 months

Population: Dose-determining population included all participants in the dose-escalation part who have received ≥75% (21 days) of the study drug and completed safety evaluations through Cycle 1 Day 28 or experienced a DLT.

MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=51 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib MTD	—	400 mg	—	—	—	—	—	—	—
Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib RP2D	—	400 mg	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years)

Population: Safety Population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in the SAP, safety data was to be analyzed and reported as per the pre-planned grouped dose level II (SAP section 3.6.5.2). Hence, per dose safety data is not presented for this study.

An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=37 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=540 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=9 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=590 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) AEs	—	37 percentage of participants	540 percentage of participants	9 percentage of participants	590 percentage of participants	—	—	—	—
Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) SAEs	—	26 percentage of participants	381 percentage of participants	7 percentage of participants	416 percentage of participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who had measurable (target) disease per RECIST v1.1 at baseline according to blinded central review (BICR) and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are also included in Phase 2 efficacy analysis.

ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=13 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=60 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=72 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=27 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=28 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=21 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Overall Response Rate (ORR)	7.7 percentage of participants Interval 0.99 to 36.0	63.1 percentage of participants Interval 54.2 to 71.4	73.9 percentage of participants Interval 51.6 to 89.8	78.3 percentage of participants Interval 69.2 to 85.7	56.7 percentage of participants Interval 43.2 to 69.4	77.8 percentage of participants Interval 66.4 to 86.7	85.2 percentage of participants Interval 66.3 to 95.8	46.4 percentage of participants Interval 27.5 to 66.1	19.0 percentage of participants Interval 5.4 to 41.9

SECONDARY outcome

Timeframe: Up to approximately 28 months

Population: Efficacy population included all participants who have been exposed to at least one dose of the study drug on or prior to 11 July 2019.

ORR was defined as the percentage of participants with a confirmed CR or PR for at least two assessments with at least 28 days apart and no PD in between. Per RECIST v1.1, CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), was presented.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=4 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=5 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: ORR	75.0 percentage of participants Interval 19.4 to 99.4	0 percentage of participants The 95% confidence interval (CI) was not estimable due to insufficient number of participants with events.	50.0 percentage of participants Interval 11.8 to 88.2	40.0 percentage of participants Interval 5.3 to 85.3	38.5 percentage of participants Interval 13.9 to 68.4	45.5 percentage of participants Interval 16.7 to 76.6	41.7 percentage of participants Interval 15.2 to 72.3	25.0 percentage of participants Interval 0.99 to 80.6	80.0 percentage of participants Interval 28.4 to 99.5

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., Kinesin family member 5B (KIF5B), coiled-coil domain containing 6 (CCDC6), nuclear receptor coactivator 4 (NCOA4)). RET genotypes were determined by local testing and/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status Other	—	46.2 percentage of participants Interval 19.2 to 74.9	0 percentage of participants The 95% CI was not estimable due to insufficient number of participants with events.	63.6 percentage of participants Interval 30.8 to 89.1	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status KIF5B	—	63.7 percentage of participants Interval 53.0 to 73.6	82.4 percentage of participants Interval 56.6 to 96.2	78.9 percentage of participants Interval 68.1 to 87.5	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status CCDC6	—	68.0 percentage of participants Interval 46.5 to 85.1	75.0 percentage of participants Interval 19.4 to 99.4	84.2 percentage of participants Interval 60.4 to 96.6	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=60 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=72 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status Other	—	100 percentage of participants Interval 39.8 to 100.0	66.7 percentage of participants Interval 9.4 to 99.2	—	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status M918T	—	53.7 percentage of participants Interval 37.4 to 69.3	74.4 percentage of participants Interval 58.8 to 86.5	—	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status Cysteine Rich Domain	—	46.2 percentage of participants Interval 19.2 to 74.9	88.0 percentage of participants Interval 68.8 to 97.5	—	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status V804X	—	100 percentage of participants Interval 15.8 to 100.0	0 percentage of participants Since only 1 participant was analyzed upper and lower limit of 95% CI was not evaluable.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in both MTC and differentiated TC (DTC). These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=27 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status CCDC6	—	82.4 percentage of participants Interval 56.6 to 96.2	—	—	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 54.1 to 100.0	—	—	—	—	—	—	—
Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status Other	—	75.0 percentage of participants Interval 19.4 to 99.4	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or stable disease (SD) which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status KIF5B	—	76.9 percentage of participants Interval 66.9 to 85.1	88.2 percentage of participants Interval 63.6 to 98.5	81.6 percentage of participants Interval 71.0 to 89.5	—	—	—	—	—
Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status CCDC6	—	76.0 percentage of participants Interval 54.9 to 90.6	75.0 percentage of participants Interval 19.4 to 99.4	84.2 percentage of participants Interval 60.4 to 96.6	—	—	—	—	—
Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—	—
Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status Other	—	53.8 percentage of participants Interval 25.1 to 80.8	0 percentage of participants The 95% CI was not estimable due to insufficient number of participants with events.	63.6 percentage of participants Interval 30.8 to 89.1	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=60 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=72 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status V804X	—	100 percentage of participants Interval 15.8 to 100.0	100 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—
Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status Other	—	100 percentage of participants Interval 39.8 to 100.0	100 percentage of participants Interval 29.2 to 100.0	—	—	—	—	—	—
Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status M918T	—	78.0 percentage of participants Interval 62.4 to 89.4	86.0 percentage of participants Interval 72.1 to 94.7	—	—	—	—	—	—
Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status Cysteine Rich Domain	—	76.9 percentage of participants Interval 46.2 to 95.0	96.0 percentage of participants Interval 79.6 to 99.9	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=27 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status Other	—	75.0 percentage of participants Interval 19.4 to 99.4	—	—	—	—	—	—	—
Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status CCDC6	—	82.4 percentage of participants Interval 56.6 to 96.2	—	—	—	—	—	—	—
Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 54.1 to 100.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status KIF5B	—	93.4 percentage of participants Interval 86.2 to 97.5	94.1 percentage of participants Interval 71.3 to 99.9	88.2 percentage of participants Interval 78.7 to 94.4	—	—	—	—	—
Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status CCDC6	—	88.0 percentage of participants Interval 68.8 to 97.5	100 percentage of participants Interval 39.8 to 100.0	89.5 percentage of participants Interval 66.9 to 98.7	—	—	—	—	—
Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—	—
Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status Other	—	84.6 percentage of participants Interval 54.6 to 98.1	50.0 percentage of participants Interval 1.3 to 98.7	100 percentage of participants Interval 71.5 to 100.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=60 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=72 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status V804X	—	100 percentage of participants Interval 15.8 to 100.0	100 percentage of participants Interval 2.5 to 100.0	—	—	—	—	—	—
Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status M918T	—	95.1 percentage of participants Interval 83.5 to 99.4	90.7 percentage of participants Interval 77.9 to 97.4	—	—	—	—	—	—
Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status Cysteine Rich Domain	—	92.3 percentage of participants Interval 64.0 to 99.8	96.0 percentage of participants Interval 79.6 to 99.9	—	—	—	—	—	—
Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status Other	—	100 percentage of participants Interval 39.8 to 100.0	100 percentage of participants Interval 29.2 to 100.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=27 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status Other	—	100 percentage of participants Interval 39.8 to 100.0	—	—	—	—	—	—	—
Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status CCDC6	—	94.1 percentage of participants Interval 71.3 to 99.9	—	—	—	—	—	—	—
Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status NCOA4	—	100 percentage of participants Interval 54.1 to 100.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR \& sufficient evidence of a RET alteration. As prespecified in SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Participants who had a response of CR/PR were analyzed in this outcome measure. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5), CCDC6, NCOA4). RET genotypes were determined by local testing &/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR=disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study. DOR was analyzed using the Kaplan-Meier (KM) method.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=82 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=17 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=83 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status KIF5B	—	15.1 months Interval 8.8 to 34.2	21.5 months Interval 9.3 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	9.2 months Interval 7.4 to 13.4	—	—	—	—	—
Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status CCDC6	—	46.7 months Interval 33.7 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	29.6 months Interval 11.3 to 47.9	NA months Interval 14.7 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—
Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status NCOA4	—	12.9 months The upper and lower limits of 95% CI were not estimable due to insufficient number of participants with events.	—	—	—	—	—	—	—
Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status Other	—	35.2 months Interval 10.6 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	41.2 months Interval 27.9 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR \& sufficient evidence of a RET alteration. As prespecified in SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Participants who had a response of CR/PR were analyzed in this outcome measure. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the Kaplan-Meier (KM) method.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=34 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=56 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status M918T	—	18.4 months Interval 15.1 to 25.8	51.8 months Interval 40.0 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—
Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status Cysteine Rich Domain	—	29.5 months Interval 8.8 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	36.8 months Interval 23.1 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—
Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status V804X	—	21.8 months Interval 14.2 to 29.4	—	—	—	—	—	—	—
Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status Other	—	NA months Interval 14.5 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR \& sufficient evidence of a RET alteration. As prespecified in SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Participants who had a response of CR/PR were analyzed in this outcome measure. Number analyzed is the number of participants with the specified mutation.

Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the KM method.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status CCDC6	—	NA months Interval 11.2 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—	—
Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status NCOA4	—	15.2 months Interval 6.9 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—	—
Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status Other	—	NA months Interval 23.6 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR \& sufficient evidence of a RET alteration. As prespecified in SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Participants who had a response of CR/PR were analyzed in this OM.

DOR was defined as the time from first documented response (CR/PR) to the date of first documented PD or death due to any cause, whichever occurs first. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DOR was analyzed using the KM methods.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=1 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=82 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=17 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=83 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=34 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=56 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=23 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=13 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=4 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: DOR	5.5 months The 95% CI was not estimable due to insufficient number of participants with events.	31.8 months Interval 15.1 to 40.4	22.6 months Interval 11.1 to 47.9	13.4 months Interval 9.4 to 21.7	21.7 months Interval 15.1 to 34.8	51.8 months Interval 36.8 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA months Interval 12.9 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	11.1 months Interval 5.5 to 25.1	NA months Interval 6.0 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

CBR was defined as the percentage of participants with CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). CBR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=13 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=60 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=72 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=27 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=28 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=21 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: CBR	23.1 percentage of participants Interval 5.0 to 53.8	74.6 percentage of participants Interval 66.2 to 81.8	78.3 percentage of participants Interval 56.3 to 92.5	80.2 percentage of participants Interval 71.3 to 87.3	80.0 percentage of participants Interval 67.7 to 89.2	90.3 percentage of participants Interval 81.0 to 96.0	85.2 percentage of participants Interval 66.3 to 95.8	60.7 percentage of participants Interval 40.6 to 78.5	28.6 percentage of participants Interval 11.3 to 52.2

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

DCR was defined as the percentage of participants with a confirmed CR/PR, or SD, per RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DCR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=13 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=130 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=23 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=106 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=60 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=72 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=27 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=28 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=21 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: DCR	69.2 percentage of participants Interval 38.6 to 90.9	91.5 percentage of participants Interval 85.4 to 95.7	91.3 percentage of participants Interval 72.0 to 98.9	89.6 percentage of participants Interval 82.2 to 94.7	95.0 percentage of participants Interval 86.1 to 99.0	93.1 percentage of participants Interval 84.5 to 97.7	96.3 percentage of participants Interval 81.0 to 99.9	75.0 percentage of participants Interval 55.1 to 89.3	42.9 percentage of participants Interval 21.8 to 66.0

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: Efficacy population included all participants who have been exposed to at least one dose of the study drug at the RP2D. As pre-specified in the SAP, PFS was to be assessed in participants with RET-fusion positive NSCLC, RET-mutation MTC, RET-fusion TC, and RET-fusion solid tumors other than NSCLC and TC. Hence, only the data for these arms is presented here. Overall number analyzed is the number of participants with data available for analysis.

PFS was defined as the time from the first dose of pralsetinib to the date of first documented PD or death due to any cause, whichever occurred first. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). PFS was analyzed using KM methods.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=141 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=24 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=116 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=67 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=78 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=31 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=28 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Progression-free Survival (PFS)	—	16.4 months Interval 11.4 to 23.5	13.0 months Interval 9.3 to 35.1	12.1 months Interval 9.2 to 16.6	24.9 months Interval 19.9 to 35.0	55.3 months Interval 37.2 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA months Interval 14.7 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	7.0 months Interval 3.9 to 12.8	—

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: Efficacy population included all participants who have been exposed to at least one dose of the study drug at the RP2D. As pre-specified in the SAP, OS was to be assessed in participants with RET-fusion positive NSCLC, RET-mutation MTC, RET-fusion TC, and RET-fusion solid tumors other than NSCLC and TC. Hence, only the data for these arms is presented here.

OS was defined as the time from the first dose of pralsetinib to the date of death due to any causes.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=141 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=24 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=116 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=67 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=78 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=31 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=29 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Overall Survival (OS)	—	39.7 months Interval 27.8 to 53.2	46.0 months Interval 19.1 to 62.4	50.1 months Interval 28.3 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	42.2 months Interval 31.2 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.	NA months Interval 19.4 to The median and upper limit of 95% CI was not estimable due to insufficient number of participants with events.	10.3 months Interval 6.8 to 25.2	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As specified in the SAP, ORR was to be assessed in RET-fusion CNS metastases sub-population (participants with CNS metastases) only. Hence only NSCLC arms are presented here. Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

ORR=percentage of participants with CR or PR for at least 2 assessments with at least 28 days apart & no PD in between. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem &/or cerebellum identified at baseline & disappearance of all non-target CNS/brain lesion at baseline & no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline & if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. PD=either at least 20% increase in the SOD of target CNS/brain lesion, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of any CNS/brain lesion identified as RECIST 1.1 nontarget lesions at baseline, or the identification of new CNS/brain lesion.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=13 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Intracranial ORR in RET-fusion Positive NSCLC Central Nervous System (CNS) Metastases Participants	—	53.8 percentage of participants Interval 25.1 to 80.8	100 percentage of participants Interval 2.5 to 100.0	0 percentage of participants The 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As specified in the SAP, CBR was to be assessed in RET-fusion CNS metastases sub-population (participants with CNS metastases) only. Hence only NSCLC arms are presented here. Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

CBR=percentage of participants with CR/PR/SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in 1 cycle) from first dose date. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem &/ cerebellum identified at baseline&disappearance of all non-target CNS/brain lesion at baseline & no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as target lesions at baseline & if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. SD=neither sufficient shrinkage for PR nor sufficient increase for PD for target/non-target CNS/brain lesion, taking as reference smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=13 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Intracranial CBR in RET-fusion Positive NSCLC CNS Metastases Participants	—	61.5 percentage of participants Interval 31.6 to 86.1	100 percentage of participants Interval 2.5 to 100.0	0 percentage of participants The 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As specified in the SAP, DCR was to be assessed in RET-fusion CNS metastases sub-population (participants with CNS metastases) only. Hence only NSCLC arms are presented here. Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

DCR=percentage of participants with a confirmed CR/PR, or SD. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem &/or cerebellum identified at baseline & disappearance of all non-target CNS/brain lesion at baseline & no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline & if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target/non-target CNS/brain lesion, taking as reference the smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=13 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Intracranial DCR in RET-fusion Positive NSCLC CNS Metastases Participants	—	76.9 percentage of participants Interval 46.2 to 95.0	100 percentage of participants Interval 2.5 to 100.0	0 percentage of participants The 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 79.8 months

Population: RET-altered measurable disease population=participants in efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR\&sufficient evidence of a RET alteration. As specified in SAP, DOR was to be assessed in RET-fusion CNS metastases sub-population only. Hence only NSCLC arms are presented here. Participants with a CR/PR were assessed for this OM. Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis.

DOR=time from first documented CR/PR to the date of first documented PD/death due to any cause, whichever occurs first. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem &/ cerebellum identified at baseline & disappearance of all non-target CNS/brain lesion at baseline & no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline & if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion. DOR was analyzed using the KM methods.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=7 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Intracranial DOR in RET-fusion Positive NSCLC CNS Metastases Participants	—	28.3 months Interval 10.5 to The upper limit of 95% CI was not estimable due to insufficient number of participants with events.	11.3 months The 95% CI was not estimable due to insufficient number of participants with events.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: Pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=3 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=6 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Maximum Plasma Concentration (Cmax) Cycle 1 Day 1	715 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 64.1	346 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	335 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 52.8	198 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 99.8	459 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 52.3	688 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 53.3	1210 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 85.3	1820 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 63.8	569 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 42.0
Phase 1: Maximum Plasma Concentration (Cmax) Cycle 1 Day 15	1780 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	130 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	420 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 56.9	586 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 47.8	525 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 72.5	1390 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 35.3	1930 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 66.7	4330 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	1080 nanograms per milliliters (ng/mL) Geometric Coefficient of Variation 43.8

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=3 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=6 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Time to Maximum Plasma Concentration (Tmax) Cycle 1 Day 1	12.0 hour Interval 2.07 to 12.3	3.04 hour Interval 2.08 to 4.0	2.04 hour Interval 1.98 to 4.0	2.03 hour Interval 2.0 to 6.03	2.07 hour Interval 0.983 to 7.98	2.02 hour Interval 1.72 to 7.9	3.00 hour Interval 2.0 to 6.03	2.00 hour Interval 2.0 to 2.0	12.5 hour Interval 12.2 to 14.8
Phase 1: Time to Maximum Plasma Concentration (Tmax) Cycle 1 Day 15	4.03 hour Interval 1.98 to 6.08	1.87 hour Interval 1.87 to 1.87	2.00 hour Interval 1.97 to 4.13	3.97 hour Interval 3.9 to 4.0	2.97 hour Interval 1.05 to 4.08	2.23 hour Interval 0.983 to 24.0	3.03 hour Interval 2.0 to 7.85	6.00 hour Interval 4.0 to 8.0	2.00 hour Interval 0.5 to 3.95

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=3 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=6 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Time of Last Quantifiable Plasma Drug Concentration (Tlast) Cycle 1 Day 1	12.3 hours Interval 12.0 to 14.4	24.0 hours Interval 24.0 to 24.0	24.0 hours Interval 23.1 to 24.4	24.0 hours Interval 7.88 to 24.1	24.0 hours Interval 21.9 to 25.7	23.8 hours Interval 7.88 to 24.0	23.8 hours Interval 22.6 to 24.6	23.9 hours Interval 23.4 to 24.0	12.5 hours Interval 12.2 to 14.8
Phase 1: Time of Last Quantifiable Plasma Drug Concentration (Tlast) Cycle 1 Day 15	12.5 hours Interval 10.1 to 14.8	23.8 hours Interval 23.8 to 23.8	24.1 hours Interval 23.9 to 24.4	24.3 hours Interval 23.6 to 27.8	24.0 hours Interval 8.0 to 26.6	24.0 hours Interval 22.2 to 24.8	24.0 hours Interval 7.38 to 25.4	24.1 hours Interval 24.0 to 24.2	12.2 hours Interval 7.88 to 15.7

SECONDARY outcome

Timeframe: 24 hours postdose on Day 1 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=6 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=8 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=3 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)	—	4450 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	3620 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 50.8	3010 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 84.8	5260 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 46.2	8470 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 54.5	14700 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 60.3	27700 hours*nanograms/milliliter (hours*ng/ml) Geometric Coefficient of Variation 94.1	—

SECONDARY outcome

Timeframe: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=9 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=8 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=3 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Plasma Drug Concentration at 24 Hours Postdose (C24hr) Cycle 1 Day 1	—	110 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	69.2 ng/mL Geometric Coefficient of Variation 81.0	65.8 ng/mL Geometric Coefficient of Variation 59.6	104 ng/mL Geometric Coefficient of Variation 76.6	221 ng/mL Geometric Coefficient of Variation 64.2	376 ng/mL Geometric Coefficient of Variation 74.1	715 ng/mL Geometric Coefficient of Variation 75.9	—
Phase 1: Plasma Drug Concentration at 24 Hours Postdose (C24hr) Cycle 1 Day 15	—	55.9 ng/mL Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	94.2 ng/mL Geometric Coefficient of Variation 123	175 ng/mL Geometric Coefficient of Variation 31.3	137 ng/mL Geometric Coefficient of Variation 132	713 ng/mL Geometric Coefficient of Variation 42.2	977 ng/mL Geometric Coefficient of Variation 107	1950 ng/mL Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=10 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=5 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=7 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=3 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Apparent Volume of Distribution (Vz/F) Cycle 1 Day 1	—	96.1 liters Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	230 liters Geometric Coefficient of Variation 37.1	458 liters Geometric Coefficient of Variation 125	499 liters Geometric Coefficient of Variation 50.8	543 liters Geometric Coefficient of Variation 82.6	430 liters Geometric Coefficient of Variation 62.6	350 liters Geometric Coefficient of Variation 115	—
Phase 1: Apparent Volume of Distribution (Vz/F) Cycle 1 Day 15	—	355 liters Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	171 liters Geometric Coefficient of Variation 176	232 liters Geometric Coefficient of Variation 43.7	622 liters Geometric Coefficient of Variation 67.3	367 liters Geometric Coefficient of Variation 86.6	418 liters Geometric Coefficient of Variation 19.9	181 liters Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=1 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=10 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=5 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=7 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=3 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Terminal Elimination Half-Life (t½) Cycle 1 Day 15	—	17.6 hours Interval 17.6 to 17.6	8.10 hours Interval 5.25 to 39.6	13.4 hours Interval 12.5 to 14.4	13.2 hours Interval 10.1 to 21.8	20.4 hours Interval 9.91 to 27.3	20.9 hours Interval 9.21 to 33.6	13.0 hours Interval 13.0 to 13.0	—
Phase 1: Terminal Elimination Half-Life (t½) Cycle 1 Day 1	10.7 hours Interval 10.7 to 10.7	16.3 hours Interval 11.8 to 20.8	9.87 hours Interval 8.98 to 18.3	14.3 hours Interval 8.12 to 31.5	12.6 hours Interval 6.69 to 34.9	12.2 hours Interval 9.53 to 34.5	16.5 hours Interval 10.2 to 48.7	19.7 hours Interval 12.8 to 36.1	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=10 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=9 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=8 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=3 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Apparent Oral Clearance (CL/F) Cycle 1 Day 1	—	4.26 liters per hour (L/hr) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	14.7 liters per hour (L/hr) Geometric Coefficient of Variation 42.3	20.6 liters per hour (L/hr) Geometric Coefficient of Variation 48.1	27.3 liters per hour (L/hr) Geometric Coefficient of Variation 60.3	23.3 liters per hour (L/hr) Geometric Coefficient of Variation 40.2	15.2 liters per hour (L/hr) Geometric Coefficient of Variation 88.1	11.6 liters per hour (L/hr) Geometric Coefficient of Variation 81.3	—
Phase 1: Apparent Oral Clearance (CL/F) Cycle 1 Day 15	—	14.0 liters per hour (L/hr) Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	11.3 liters per hour (L/hr) Geometric Coefficient of Variation 51.2	12.0 liters per hour (L/hr) Geometric Coefficient of Variation 38.9	31.4 liters per hour (L/hr) Geometric Coefficient of Variation 97.8	13.2 liters per hour (L/hr) Geometric Coefficient of Variation 33.0	11.1 liters per hour (L/hr) Geometric Coefficient of Variation 72.2	8.57 liters per hour (L/hr) Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	—

SECONDARY outcome

Timeframe: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=1 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=12 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=9 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=10 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=2 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=4 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Accumulation Ratio for Cmax (RCmax)	1.41 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.04 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.25 ratio Geometric Coefficient of Variation 27.6	3.20 ratio Geometric Coefficient of Variation 114	1.17 ratio Geometric Coefficient of Variation 110	1.87 ratio Geometric Coefficient of Variation 40.5	1.62 ratio Geometric Coefficient of Variation 102	2.97 ratio Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.	1.91 ratio Geometric Coefficient of Variation 40.7

SECONDARY outcome

Timeframe: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis.

Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=1 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=8 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=6 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=1 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=2 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Accumulation Ratio for AUC (RAUC)	1.21 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.43 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.47 ratio Geometric Coefficient of Variation 11.1	3.22 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.31 ratio Geometric Coefficient of Variation 147	2.33 ratio Geometric Coefficient of Variation 11.4	2.75 ratio Geometric Coefficient of Variation 70.9	2.48 ratio Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	4.28 ratio Geometric Coefficient of Variation NA Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not evaluable.

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=98 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Cmax Cycle 1 Day 1	—	1680 ng/mL Geometric Coefficient of Variation 69.4	1380 ng/mL Geometric Coefficient of Variation 65.4	2450 ng/mL Geometric Coefficient of Variation 164	1770 ng/mL Geometric Coefficient of Variation 87.2	—	—	—	—
Phase 2: Cmax Cycle 1 Day 15	—	2840 ng/mL Geometric Coefficient of Variation 50.7	2200 ng/mL Geometric Coefficient of Variation 36.7	3440 ng/mL Geometric Coefficient of Variation 93.9	2430 ng/mL Geometric Coefficient of Variation 55.3	—	—	—	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=98 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Tmax Cycle 1 Day 1	—	4.00 hours Interval 1.9 to 23.7	3.90 hours Interval 2.0 to 6.0	4.0 hours Interval 4.0 to 6.0	2.05 hours Interval 2.0 to 8.0	—	—	—	—
Phase 2: Tmax Cycle 1 Day 15	—	4.00 hours Interval 1.0 to 8.1	5.00 hours Interval 2.0 to 8.0	4.00 hours Interval 2.0 to 6.0	3.05 hours Interval 2.0 to 6.0	—	—	—	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=98 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: Tlast Cycle 1 Day 1	—	23.9 hours Interval 2.4 to 24.8	8.00 hours Interval 7.8 to 23.5	23.10 hours Interval 8.0 to 24.0	8.05 hours Interval 8.0 to 24.0	—	—	—	—
Phase 2: Tlast Cycle 1 Day 15	—	23.8 hours Interval 7.8 to 26.5	23.70 hours Interval 7.9 to 24.0	24.00 hours Interval 7.9 to 24.0	24.00 hours Interval 23.8 to 24.0	—	—	—	—

SECONDARY outcome

Timeframe: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=70 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=3 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: AUC0-24 Cycle 1 Day 1	—	20400 hours*ng/mL Geometric Coefficient of Variation 64.2	17400 hours*ng/mL Geometric Coefficient of Variation 152	103000 hours*ng/mL Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	18400 hours*ng/mL Geometric Coefficient of Variation 69.8	—	—	—	—
Phase 2: AUC0-24 Cycle 1 Day 15	—	40100 hours*ng/mL Geometric Coefficient of Variation 59.5	33900 hours*ng/mL Geometric Coefficient of Variation 27.4	91100 hours*ng/mL Geometric Coefficient of Variation 46.8	32000 hours*ng/mL Geometric Coefficient of Variation 90.8	—	—	—	—

SECONDARY outcome

Timeframe: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=92 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=5 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=3 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=4 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: C24hr Cycle 1 Day 1	—	540 ng/mL Geometric Coefficient of Variation 75.4	519 ng/mL Geometric Coefficient of Variation 197	1020 ng/mL Geometric Coefficient of Variation 225	415 ng/mL Geometric Coefficient of Variation 140	—	—	—	—
Phase 2: C24hr Cycle 1 Day 15	—	1150 ng/mL Geometric Coefficient of Variation 69	797 ng/mL Geometric Coefficient of Variation 42.8	1400 ng/mL Geometric Coefficient of Variation 207	1050 ng/mL Geometric Coefficient of Variation 94.0	—	—	—	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=57 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=3 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: t½ Cycle 1 Day 15	—	17.9 hours Geometric Coefficient of Variation 58.8	16.5 hours Geometric Coefficient of Variation 44.6	25.8 hours Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	63.0 hours Geometric Coefficient of Variation 882	—	—	—	—
Phase 2: t½ Cycle 1 Day 1	—	13.4 hours Geometric Coefficient of Variation 44.1	18.4 hours Geometric Coefficient of Variation 98.8	20.8 hours Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	11.0 hours Geometric Coefficient of Variation 55.8	—	—	—	—

SECONDARY outcome

Timeframe: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

Population: PK evaluable population included all participants who received at least one dose of pralsetinib and from whom at least one post dose PK sample was collected. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=47 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=1 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=3 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 2: CL/F Cycle 1 Day 15	—	9.91 liters per hour (L/hour) Geometric Coefficient of Variation 58.9	7.49 liters per hour (L/hour) Geometric Coefficient of Variation 64.4	2.92 liters per hour (L/hour) Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	1.39 liters per hour (L/hour) Geometric Coefficient of Variation 1220	—	—	—	—
Phase 2: CL/F Cycle 1 Day 1	—	13.4 liters per hour (L/hour) Geometric Coefficient of Variation 56.8	12.7 liters per hour (L/hour) Geometric Coefficient of Variation 347	2.00 liters per hour (L/hour) Geometric Coefficient of Variation NA Since data was available only for 1 participant geometric co-efficient of variation was not evaluable.	16.1 liters per hour (L/hour) Geometric Coefficient of Variation 43.3	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Safety Population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels.

The dose dependent change in a mitogen-activated protein kinases (MAPK) pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker DUSP6 levels was explored.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=4 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=5 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Percent Change From Baseline in Dual Specificity Phosphatase 6 (DUSP6)	-61.96 percent change Standard Deviation 39.141	0 percent change Standard Deviation 0	54.26 percent change Standard Deviation 88.318	0 percent change Standard Deviation 0	-20.27 percent change Standard Deviation 42.971	-74.87 percent change Standard Deviation 15.707	-13.32 percent change Standard Deviation 82.394	0 percent change Standard Deviation 0	-81.57 percent change Standard Deviation 3.057

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Safety Population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels.

The dose dependent change in a MAPK pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker SPRY4 levels was explored.

Outcome measures

Measure	RET-mutation Positive Tumors Other Than MTC n=4 Participants Participants who had RET-mutation positive solid tumors received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET- Fusion Positive NSCLC With Prior Platinum Treatment n=2 Participants Participants who had RET-fusion positive NSCLC previously treated with platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With Non-platinum Systemic Treatment n=6 Participants Participants who had RET-fusion positive NSCLC previously treated with non-platinum or systemic therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive NSCLC With No Prior Systemic or Platinum Treatment n=5 Participants Participants who had RET-fusion positive NSCLC not previously treated with systemic or platinum-based chemotherapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With Prior Cabozantinib and/or Vandetanib Treatment n=13 Participants Participants who had RET- mutation positive MTC previously treated with either cabozantinib and/or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-mutation MTC With No Prior Cabozantinib or Vandetanib Treatment n=11 Participants Participants who had RET- mutation positive MTC not previously treated with cabozantinib or vandetanib therapies received pralsetinib, 400 mg orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive TC n=12 Participants Participants who had RET-fusion positive TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-fusion Positive Solid Tumors Other Than NSCLC and TC n=4 Participants Participants who had other RET-positive solid tumors other than NSCLC and TC received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	RET-altered Solid Tumors Previously Treated With RET Inhibitor n=5 Participants Participants who had RET-altered (fusion or mutation) solid tumors previously treated with a selective RET TKI received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.
Phase 1: Percent Change From Baseline in Sprout Receptor Tyrosine Kinase Signaling Antagonist 4 (SPRY4)	124.93 percent change Standard Deviation 311.210	0 percent change Standard Deviation 0	210.16 percent change Standard Deviation 309.468	0 percent change Standard Deviation 0	-34.98 percent change Standard Deviation 29.569	-69.00 percent change Standard Deviation 28.731	-3.26 percent change Standard Deviation 99.349	0 percent change Standard Deviation 0	-75.65 percent change Standard Deviation 10.944

Adverse Events

Pralsetinib ≤ 300 mg QD

Serious events: 26 serious events

Other events: 36 other events

Deaths: 15 deaths

Pralsetinib 400 mg QD

Serious events: 381 serious events

Other events: 536 other events

Deaths: 245 deaths

Pralsetinib BID Dosing Schedule

Serious events: 7 serious events

Other events: 9 other events

Deaths: 7 deaths

Pralsetinib All Doses

Serious events: 416 serious events

Other events: 585 other events

Deaths: 268 deaths

Serious adverse events

Measure	Pralsetinib ≤ 300 mg QD n=37 participants at risk Participants received pralsetinib, 300 mg or less, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib 400 mg QD n=540 participants at risk Participants received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib BID Dosing Schedule n=9 participants at risk Participants received pralsetinib, 100 mg, orally, BID or 200 mg in the morning and then 100 mg in the evening, orally, until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib All Doses n=590 participants at risk Participants received pralsetinib at varying doses at the QD and BID schedule until discontinuation due to toxicity, disease progression, or other reasons.
Blood and lymphatic system disorders Anaemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.9% 32/540 • Number of events 50 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.8% 34/590 • Number of events 52 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Anaemia macrocytic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Anaemia of malignant disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Bicytopenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Eosinophilia	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Leukocytosis	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Neutropenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 62 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 62 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Acute myocardial infarction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Angina pectoris	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Atrioventricular block complete	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Bradycardia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Cardiac arrest	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Cardiac discomfort	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Cardiac failure congestive	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Myocardial infarction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Myocardial injury	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Pericardial effusion	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Stress cardiomyopathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Supraventricular tachycardia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Ear and labyrinth disorders Vertigo	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Endocrine disorders Adrenal insufficiency	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Endocrine disorders Hypercalcaemia of malignancy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Eye disorders Keratitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal distension	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal mass	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Ascites	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Colitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Constipation	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Diarrhoea	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 9/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Dysphagia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Haematemesis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Haematochezia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Large intestine perforation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Melaena	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Nausea	5.4% 2/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Noninfective sialoadenitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Oesophagitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Pneumoperitoneum	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Proctitis ulcerative	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Rectal haemorrhage	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Stomatitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Vomiting	5.4% 2/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Asthenia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Calcinosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Condition aggravated	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Death	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Disease progression	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 10/540 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 10/590 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Drug withdrawal syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Face oedema	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Fatigue	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders General physical health deterioration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Granuloma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Impaired healing	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Malaise	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Multiple organ dysfunction syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Non-cardiac chest pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Oedema peripheral	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Performance status decreased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Pyrexia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.8% 15/540 • Number of events 21 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 21 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Bile duct stone	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholangitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholangitis acute	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholecystitis	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Cholelithiasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Hepatic failure	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Hyperbilirubinaemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Hypertransaminasaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Liver disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Liver injury	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Hepatobiliary disorders Subcapsular hepatic haematoma	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Abdominal infection	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Acute sinusitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Appendicitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Appendicitis perforated	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Arthritis bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Arthritis infective	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Atypical mycobacterial pneumonia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Atypical pneumonia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Bacteraemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 9/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Bronchitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Bronchitis bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations COVID-19	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.0% 16/540 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.9% 17/590 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations COVID-19 pneumonia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 13/540 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 14/590 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Cellulitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Cholecystitis infective	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Clostridium difficile colitis	2.7% 1/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Coronavirus infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Cystitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Device related infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Diverticulitis	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Diverticulitis intestinal perforated	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Empyema	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Enterobacter bacteraemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Enterococcal bacteraemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Epididymitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Escherichia bacteraemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Escherichia sepsis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Escherichia urinary tract infection	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Febrile infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Gastroenteritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Haemophilus infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Hepatitis B reactivation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Herpes zoster	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Influenza	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Kidney infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Klebsiella bacteraemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Klebsiella urinary tract infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Large intestine infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Lower respiratory tract infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Lymph node tuberculosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Meningitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Meningitis bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Meningitis enterococcal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Nasopharyngitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Neutropenic sepsis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Oropharyngeal candidiasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Osteomyelitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pancreatic abscess	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Peritonitis bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pleural infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumocystis jirovecii pneumonia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia	13.5% 5/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.1% 87/540 • Number of events 120 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.9% 94/590 • Number of events 127 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia aspiration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia cytomegaloviral	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia haemophilus	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia influenzal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia legionella	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia staphylococcal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia viral	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Postoperative wound infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pseudomembranous colitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Psoas abscess	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pyelonephritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pyelonephritis acute	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Renal tuberculosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Respiratory tract infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Scrotal cellulitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Sepsis	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.7% 20/540 • Number of events 23 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.2% 25/590 • Number of events 30 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Septic arthritis staphylococcal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Septic shock	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Sinusitis aspergillus	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Sinusitis bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Skin infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Spontaneous bacterial peritonitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Streptococcal bacteraemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Tonsillitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Upper respiratory tract infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Urinary tract infection	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.3% 23/540 • Number of events 40 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.4% 26/590 • Number of events 43 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Urinary tract infection bacterial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Urinary tract infection enterococcal	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Urosepsis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Varicella	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Viral infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Chemical peritonitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Fall	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Gastroenteritis radiation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Immunisation reaction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Periprosthetic fracture	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Post procedural haemorrhage	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Procedural pneumothorax	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Radiation pneumonitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Road traffic accident	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Seroma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Spinal compression fracture	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Spinal fracture	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Alanine aminotransferase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Aspartate aminotransferase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Bilirubin conjugated increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood bilirubin increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood creatine phosphokinase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Electrocardiogram QT prolonged	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Hepatic enzyme increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Inflammatory marker increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Lymphocyte count decreased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Neutrophil count decreased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Platelet count decreased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Decreased appetite	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Dehydration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyponatraemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 10/590 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Pseudohyperkalaemia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Tumour lysis syndrome	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Chest wall haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Haematoma muscle	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 9/540 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 9/590 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Spinal disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anaplastic large-cell lymphoma	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.8% 26/540 • Number of events 30 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.6% 27/590 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Medullary thyroid cancer	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraneoplastic syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer metastatic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Ataxia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Brain oedema	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Carotid artery stenosis	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Cerebral haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Cerebral haemorrhage	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Cerebral infarction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Cerebrovascular accident	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Cognitive disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Dizziness	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Encephalopathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Epilepsy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Haemorrhage intracranial	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Headache	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Hydrocephalus	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Intracranial pressure increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Lumbar radiculopathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Malignant spinal cord compression	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Migraine	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Neuralgia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Neuropathy peripheral	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Paraesthesia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Polyneuropathy chronic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Presyncope	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Radicular pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Radiculopathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Seizure	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.3% 7/540 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Syncope	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Vertebral artery thrombosis	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Vocal cord paralysis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Product Issues Device dislocation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Product Issues Device issue	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Confusional state	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Delirium	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Depression	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Mental status changes	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Acute kidney injury	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Calculus urinary	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Haematuria	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Hydronephrosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Nephrolithiasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Obstructive nephropathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Renal colic	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Renal failure	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Renal impairment	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Ureterolithiasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Urethral stenosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Urinary retention	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Abnormal uterine bleeding	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Heavy menstrual bleeding	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Prostatitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Uterine polyp	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Chylothorax	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Cough	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 10/540 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 10/590 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Haemothorax	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.0% 11/540 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 14/590 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.4% 2/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.0% 27/540 • Number of events 32 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.9% 29/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pneumonitis aspiration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.0% 12/590 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 9/590 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Surgical and medical procedures Spinal decompression	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Deep vein thrombosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Embolism	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Hypertension	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Hypotension	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Internal haemorrhage	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Jugular vein thrombosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Orthostatic hypotension	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral embolism	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral ischaemia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral vascular disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Phlebitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Superior vena cava syndrome	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.

Other adverse events

Measure	Pralsetinib ≤ 300 mg QD n=37 participants at risk Participants received pralsetinib, 300 mg or less, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib 400 mg QD n=540 participants at risk Participants received pralsetinib, 400 mg, orally, QD until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib BID Dosing Schedule n=9 participants at risk Participants received pralsetinib, 100 mg, orally, BID or 200 mg in the morning and then 100 mg in the evening, orally, until discontinuation due to toxicity, disease progression, or other reasons.	Pralsetinib All Doses n=590 participants at risk Participants received pralsetinib at varying doses at the QD and BID schedule until discontinuation due to toxicity, disease progression, or other reasons.
Blood and lymphatic system disorders Anaemia	43.2% 16/37 • Number of events 45 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	52.8% 285/540 • Number of events 1098 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	66.7% 6/9 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	52.5% 310/590 • Number of events 1168 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Leukopenia	10.8% 4/37 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.2% 55/540 • Number of events 226 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.3% 61/590 • Number of events 239 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Lymphopenia	18.9% 7/37 • Number of events 29 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.4% 67/540 • Number of events 321 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.1% 77/590 • Number of events 359 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Neutropenia	21.6% 8/37 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	23.0% 124/540 • Number of events 422 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.9% 135/590 • Number of events 456 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Blood and lymphatic system disorders Thrombocytopenia	8.1% 3/37 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.1% 44/540 • Number of events 98 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.1% 48/590 • Number of events 105 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Left ventricular dysfunction	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Cardiac disorders Left ventricular hypertrophy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Ear and labyrinth disorders Hypoacusis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Eye disorders Corneal epithelial microcysts	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Eye disorders Eye disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Eye disorders Growth of eyelashes	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Eye disorders Vision blurred	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 34/540 • Number of events 49 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 37/590 • Number of events 52 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal discomfort	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 9/540 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 11/590 • Number of events 13 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal distension	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.0% 27/540 • Number of events 33 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.9% 29/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal pain	13.5% 5/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.6% 68/540 • Number of events 89 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.5% 74/590 • Number of events 95 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Abdominal pain upper	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.5% 46/540 • Number of events 56 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.3% 49/590 • Number of events 59 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Ascites	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.5% 19/540 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.9% 23/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Chronic gastritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Constipation	32.4% 12/37 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	44.1% 238/540 • Number of events 329 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	43.2% 255/590 • Number of events 351 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Diarrhoea	27.0% 10/37 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	35.0% 189/540 • Number of events 373 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	44.4% 4/9 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	35.1% 207/590 • Number of events 407 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Dry mouth	5.4% 2/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	17.0% 92/540 • Number of events 103 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.3% 96/590 • Number of events 110 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Dyspepsia	8.1% 3/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 29/540 • Number of events 36 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 41 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Dysphagia	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.1% 44/540 • Number of events 50 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.0% 47/590 • Number of events 53 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastritis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 10/540 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 11/590 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrointestinal wall thickening	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 34/540 • Number of events 41 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 37/590 • Number of events 44 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Mouth ulceration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 13/540 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Nausea	27.0% 10/37 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	21.1% 114/540 • Number of events 163 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	21.4% 126/590 • Number of events 182 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Paraesthesia oral	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Stomatitis	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.1% 33/540 • Number of events 53 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 37/590 • Number of events 57 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Toothache	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.6% 14/540 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Gastrointestinal disorders Vomiting	18.9% 7/37 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.3% 88/540 • Number of events 113 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.1% 95/590 • Number of events 123 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Asthenia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.3% 88/540 • Number of events 192 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.3% 90/590 • Number of events 194 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Calcinosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Chest discomfort	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.0% 16/540 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 18/590 • Number of events 21 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Chills	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.2% 28/540 • Number of events 30 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 34 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Face oedema	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.8% 42/540 • Number of events 57 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.3% 43/590 • Number of events 58 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Fatigue	32.4% 12/37 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	28.5% 154/540 • Number of events 289 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	28.6% 169/590 • Number of events 309 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Localised oedema	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Malaise	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.1% 33/540 • Number of events 44 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.8% 34/590 • Number of events 45 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Mucosal inflammation	8.1% 3/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.4% 40/540 • Number of events 56 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.3% 43/590 • Number of events 60 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Non-cardiac chest pain	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.9% 21/540 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.6% 27/590 • Number of events 28 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Oedema peripheral	24.3% 9/37 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	19.3% 104/540 • Number of events 140 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	44.4% 4/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	19.8% 117/590 • Number of events 154 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Peripheral swelling	10.8% 4/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 17/540 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.7% 22/590 • Number of events 25 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
General disorders Pyrexia	18.9% 7/37 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	30.4% 164/540 • Number of events 266 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	29.8% 176/590 • Number of events 286 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Bronchitis	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.3% 23/540 • Number of events 28 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.2% 25/590 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations COVID-19	5.4% 2/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.9% 64/540 • Number of events 71 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.2% 66/590 • Number of events 75 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Cellulitis	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 9/540 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.0% 12/590 • Number of events 13 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Ear infection	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Folliculitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Fungal foot infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Influenza	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 13/540 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Lower respiratory tract infection	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Oral candidiasis	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 17/540 • Number of events 26 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.6% 21/590 • Number of events 30 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Oropharyngeal candidiasis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.9% 64/540 • Number of events 107 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.5% 68/590 • Number of events 111 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Pneumonia aspiration	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Sinusitis	8.1% 3/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.3% 18/540 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.7% 22/590 • Number of events 24 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Skin candida	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Upper respiratory tract infection	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	9.4% 51/540 • Number of events 61 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	9.0% 53/590 • Number of events 63 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Urinary tract infection	13.5% 5/37 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	14.8% 80/540 • Number of events 167 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	14.7% 87/590 • Number of events 182 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Infections and infestations Wound infection	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Abdominal injury	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Fall	2.7% 1/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.3% 18/540 • Number of events 21 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.6% 21/590 • Number of events 26 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Incision site haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Joint injury	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Procedural nausea	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Alanine aminotransferase increased	43.2% 16/37 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	39.3% 212/540 • Number of events 459 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	39.3% 232/590 • Number of events 495 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Aspartate aminotransferase increased	45.9% 17/37 • Number of events 41 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	50.6% 273/540 • Number of events 693 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	50.0% 295/590 • Number of events 739 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood alkaline phosphatase increased	21.6% 8/37 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.6% 68/540 • Number of events 112 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.2% 78/590 • Number of events 125 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood bilirubin increased	5.4% 2/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.7% 58/540 • Number of events 166 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.3% 61/590 • Number of events 172 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood creatine phosphokinase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.0% 97/540 • Number of events 445 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.4% 97/590 • Number of events 445 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood creatinine increased	29.7% 11/37 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	26.5% 143/540 • Number of events 288 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	26.8% 158/590 • Number of events 310 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Blood lactate dehydrogenase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.7% 47/540 • Number of events 72 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.0% 47/590 • Number of events 72 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Electrocardiogram QT prolonged	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.7% 31/540 • Number of events 39 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 40 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Electrocardiogram repolarisation abnormality	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Gamma-glutamyltransferase increased	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.0% 38/540 • Number of events 108 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.4% 38/590 • Number of events 108 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Hepatic enzyme increased	5.4% 2/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Lymphocyte count decreased	16.2% 6/37 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.7% 90/540 • Number of events 345 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.6% 98/590 • Number of events 379 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Neutrophil count decreased	13.5% 5/37 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	27.0% 146/540 • Number of events 539 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	25.9% 153/590 • Number of events 558 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Platelet count decreased	8.1% 3/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.4% 67/540 • Number of events 166 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.2% 72/590 • Number of events 173 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Weight decreased	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.7% 36/540 • Number of events 50 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.4% 38/590 • Number of events 52 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations Weight increased	5.4% 2/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.5% 62/540 • Number of events 170 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.8% 64/590 • Number of events 174 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Investigations White blood cell count decreased	37.8% 14/37 • Number of events 41 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	29.1% 157/540 • Number of events 579 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	29.7% 175/590 • Number of events 636 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Decreased appetite	16.2% 6/37 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	20.9% 113/540 • Number of events 164 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	21.0% 124/590 • Number of events 175 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Dehydration	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 10/540 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.0% 12/590 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypercalcaemia	5.4% 2/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.9% 21/540 • Number of events 32 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.1% 24/590 • Number of events 36 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyperglycaemia	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.9% 37/540 • Number of events 59 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.6% 39/590 • Number of events 61 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyperkalaemia	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 29/540 • Number of events 50 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.6% 33/590 • Number of events 54 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyperphosphataemia	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.7% 101/540 • Number of events 177 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.5% 109/590 • Number of events 186 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypoalbuminaemia	13.5% 5/37 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.6% 84/540 • Number of events 228 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.1% 89/590 • Number of events 234 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypocalcaemia	18.9% 7/37 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	24.1% 130/540 • Number of events 321 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	23.4% 138/590 • Number of events 336 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypokalaemia	10.8% 4/37 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.1% 98/540 • Number of events 163 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	17.5% 103/590 • Number of events 185 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypomagnesaemia	10.8% 4/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.0% 54/540 • Number of events 105 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	9.8% 58/590 • Number of events 110 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hyponatraemia	13.5% 5/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.0% 70/540 • Number of events 122 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.4% 79/590 • Number of events 135 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Metabolism and nutrition disorders Hypophosphataemia	16.2% 6/37 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.9% 75/540 • Number of events 131 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	14.2% 84/590 • Number of events 151 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Arthralgia	18.9% 7/37 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.7% 90/540 • Number of events 118 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	33.3% 3/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.9% 100/590 • Number of events 130 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Back pain	16.2% 6/37 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.3% 88/540 • Number of events 119 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	16.1% 95/590 • Number of events 126 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Muscle spasms	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.8% 42/540 • Number of events 50 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.8% 46/590 • Number of events 54 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Muscular weakness	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.5% 19/540 • Number of events 23 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.6% 21/590 • Number of events 25 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Myalgia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.4% 67/540 • Number of events 121 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.7% 69/590 • Number of events 123 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Neck pain	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 34/540 • Number of events 39 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.1% 36/590 • Number of events 41 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Musculoskeletal and connective tissue disorders Pain in extremity	16.2% 6/37 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.2% 66/540 • Number of events 105 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	12.2% 72/590 • Number of events 111 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.0% 6/590 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.74% 4/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.85% 5/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Dizziness	18.9% 7/37 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.4% 83/540 • Number of events 101 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	15.9% 94/590 • Number of events 115 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Dysgeusia	5.4% 2/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.7% 74/540 • Number of events 97 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	13.1% 77/590 • Number of events 102 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Headache	21.6% 8/37 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.5% 100/540 • Number of events 140 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	18.6% 110/590 • Number of events 152 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Hypoaesthesia	13.5% 5/37 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.5% 35/540 • Number of events 46 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.8% 40/590 • Number of events 51 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Memory impairment	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 13/540 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 20 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Neuropathy peripheral	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.8% 26/540 • Number of events 36 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 43 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Paraesthesia	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.1% 33/540 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.6% 33/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.9% 21/540 • Number of events 26 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.7% 22/590 • Number of events 27 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Anxiety	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.2% 28/540 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Depression	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.5% 19/540 • Number of events 20 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.6% 21/590 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Psychiatric disorders Insomnia	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.7% 47/540 • Number of events 56 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.8% 52/590 • Number of events 61 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Acute kidney injury	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 17/540 • Number of events 21 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.2% 19/590 • Number of events 23 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Dysuria	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.2% 28/540 • Number of events 34 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.9% 29/590 • Number of events 35 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Renal failure	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.5% 8/540 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 10/590 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Renal and urinary disorders Urinary incontinence	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.37% 2/540 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.51% 3/590 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Breast calcifications	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Reproductive system and breast disorders Erectile dysfunction	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.6% 30/540 • Number of events 34 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	5.4% 32/590 • Number of events 36 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Cough	24.3% 9/37 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	27.6% 149/540 • Number of events 222 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	27.3% 161/590 • Number of events 236 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Dysphonia	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.7% 47/540 • Number of events 55 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	8.3% 49/590 • Number of events 57 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Dyspnoea	32.4% 12/37 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	20.7% 112/540 • Number of events 146 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	21.5% 127/590 • Number of events 165 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.1% 22/540 • Number of events 32 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.1% 24/590 • Number of events 34 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.6% 41/540 • Number of events 49 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.3% 43/590 • Number of events 51 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.5% 19/540 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.1% 24/590 • Number of events 27 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.8% 4/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.6% 41/540 • Number of events 54 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	7.6% 45/590 • Number of events 58 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.0% 16/540 • Number of events 36 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 18/590 • Number of events 38 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Pneumonitis	18.9% 7/37 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	9.4% 51/540 • Number of events 97 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.0% 59/590 • Number of events 109 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.5% 35/540 • Number of events 39 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.1% 36/590 • Number of events 40 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.7% 1/37 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Acne	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Alopecia	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 34/540 • Number of events 37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	6.3% 37/590 • Number of events 40 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Dermatitis acneiform	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.1% 17/540 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	22.2% 2/9 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.7% 22/590 • Number of events 23 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Dry skin	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.9% 21/540 • Number of events 25 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	4.2% 25/590 • Number of events 29 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.7% 9/540 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.9% 11/590 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.4% 2/37 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.0% 16/540 • Number of events 20 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	3.2% 19/590 • Number of events 25 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Perioral dermatitis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.56% 3/540 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.68% 4/590 • Number of events 4 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Rash	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.7% 58/540 • Number of events 71 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	10.3% 61/590 • Number of events 74 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Rash erythematous	8.1% 3/37 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.93% 5/540 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.4% 8/590 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.6% 14/540 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Haematoma	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.1% 6/540 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	1.2% 7/590 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Hypertension	24.3% 9/37 • Number of events 12 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	35.0% 189/540 • Number of events 499 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	44.4% 4/9 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	34.9% 206/590 • Number of events 530 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Hypotension	5.4% 2/37 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.4% 13/540 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	2.5% 15/590 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Intermittent claudication	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Peripheral vascular disorder	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Thrombosis	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.19% 1/540 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.34% 2/590 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.
Vascular disorders Vasodilatation	0.00% 0/37 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.00% 0/540 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	11.1% 1/9 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.	0.17% 1/590 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) All-cause Mortality: Up to approximately 7 years Safety population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in SAP, safety data was to be analyzed \& reported per pre-planned grouped dose level II. Per dose level II, ≤ 300 mg QD arm included participants dosed with pralsetinib at 30 mg, 60 mg , 100 mg , 200 mg \& 300 mg QD; 400 mg arm included participants dosed at 400 mg QD, BID Dosing Schedule arm included participants dosed with 100/100 mg \& 200/100 mg BID, \& All doses included participants treated at all QD \& BID doses \& 600 mg QD dose. Hence, AEs cannot be presented per dose level.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER