Trial Outcomes & Findings for Drug-Drug Interaction Study of TAK-788 and Midazolam in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (NCT NCT04051827)

NCT ID: NCT04051827

Last Updated: 2025-07-28

Results Overview

As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

26 participants

Primary outcome timeframe

Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length is equal to [=] 30 days)

Results posted on

2025-07-28

Participant Flow

Participants took part in the study at 7 investigative sites in Australia, Singapore, and Netherlands from 23 December 2019 to 07 December 2021.

Participants with a historical diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC) were enrolled in this 2-part study to receive midazolam oral solution along with mobocertinib (formerly TAK-788) capsule in Part A (Cycle 1) and mobocertinib capsule only in Part B (Cycle 2 to 19). After completion of Part A, eligible participants entered Part B to continue treatment with mobocertinib. As planned, combined safety data for Parts A and B was collected and reported.

Participant milestones

Participant milestones
Measure	Parts A and B: Midazolam + Mobocertinib Midazolam 3 milligram (mg), solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1) in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18).
Overall Study STARTED	26
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Parts A and B: Midazolam + Mobocertinib Midazolam 3 milligram (mg), solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1) in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18).
Overall Study Death	1
Overall Study Withdrawal by Subject	4
Overall Study Progressive disease	16
Overall Study Physician Decision	1
Overall Study Other	4

Baseline Characteristics

Drug-Drug Interaction Study of TAK-788 and Midazolam in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parts A and B: Midazolam + Mobocertinib n=26 Participants Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1) in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18).
Age, Continuous	61.7 years STANDARD_DEVIATION 14.62 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Australia	14 Participants n=5 Participants
Region of Enrollment Singapore	7 Participants n=5 Participants
Region of Enrollment Netherlands	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length is equal to [=] 30 days)

Population: Pharmacokinetic (PK) evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications through Day 26; and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.

As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=13 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, Cmax: Geometric Mean Maximum Observed Plasma Concentration (Cmax) for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)	17.0 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 60.2	17.5 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 60.7

PRIMARY outcome

Timeframe: Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Population: PK evaluable population. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

As planned, this PK outcome measure was only assessed in Part A.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=12 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, AUC∞: Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)	58.3 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 61.0	39.0 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 61.4

PRIMARY outcome

Timeframe: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications through Day 26; and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.

As planned, this PK outcome measure was only assessed in Part A.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=13 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, Cmax: Geometric Mean Maximum Observed Plasma Concentration (Cmax) for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)	70.8 ng/mL Geometric Coefficient of Variation 151.0	92.2 ng/mL Geometric Coefficient of Variation 132.0

PRIMARY outcome

Timeframe: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Population: PK evaluable population. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

As planned, this PK outcome measure was only assessed in Part A.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=12 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, AUC∞: Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)	90.4 ng*h/mL Geometric Coefficient of Variation 113.0	71.6 ng*h/mL Geometric Coefficient of Variation 96.0

PRIMARY outcome

Timeframe: Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications till completion of PK sampling (Day 26); and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.

As planned, this PK outcome measure was only assessed in Part A for midazolam 3 mg oral solution.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=13 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)	0.517 hour Interval 0.467 to 2.0	0.533 hour Interval 0.25 to 1.0

PRIMARY outcome

Timeframe: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications till completion of PK sampling (Day 26); and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.

As planned, this PK outcome measure was only assessed in Part A for midazolam 1 mg intravenous infusion.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=13 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib n=13 Participants Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)	0.0500 hour Interval 0.0 to 1.0	0.0500 hour Interval 0.0 to 0.5

SECONDARY outcome

Timeframe: Part A:From Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months);Part B:From Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) (Cycle length, Part A= 30 days; Part B=28 days)

Population: The safety population was defined as all participants who received at least 1 dose of any study drug (mobocertinib or midazolam). Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=26 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A and B: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	26 Participants	—

SECONDARY outcome

Timeframe: Part A: Day 1 of Cycle 1; Part B: Day 1 of every Cycle (Cycle 2 to Cycle 19) (Cycle length, Part A=30 days; Part B =28 days)

The clinically significant change from baseline in laboratory values was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=26 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values Blood creatinine increased	7 Participants	—
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values Amylase increased	3 Participants	—
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values Lipase increased	3 Participants	—

SECONDARY outcome

Timeframe: Part A: Day 1 up to Day 26 in Cycle 1; Part B: Day 1 of every Cycle (Cycle 2 to Cycle 19) (Cycle length, Part A=30 days; Part B =28 days)

Outcome measures

Outcome measures
Measure	Part A: Midazolam Alone n=26 Participants Midazolam 3 mg, solution, orally, once on Day 1 in Cycle 1 (Month 1).	Part A: Midazolam + Mobocertinib Midazolam 3 mg, solution, orally, once on Day 24 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1).
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 Participants	—

Adverse Events

Parts A and B: Midazolam + Mobocertinib

Serious events: 20 serious events

Other events: 26 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Parts A and B: Midazolam + Mobocertinib n=26 participants at risk Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18).
Cardiac disorders Arrhythmia	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Cerebrovascular accident	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Dehydration	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Diarrhoea	23.1% 6/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hypercalcaemia	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Ileus	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Nausea	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Pneumonia	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
General disorders Pyrexia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Respiratory tract infection	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Sepsis	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Spinal cord compression	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Urinary tract infection	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Renal and urinary disorders Urinary tract obstruction	3.8% 1/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Vomiting	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).

Other adverse events

Other adverse events
Measure	Parts A and B: Midazolam + Mobocertinib n=26 participants at risk Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18).
Gastrointestinal disorders Abdominal pain	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Renal and urinary disorders Acute kidney injury	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Alopecia	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Investigations Amylase increased	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Blood and lymphatic system disorders Anaemia	19.2% 5/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Angular cheilitis	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Investigations Blood creatinine increased	26.9% 7/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
General disorders Chills	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Constipation	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Cough	19.2% 5/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Decreased appetite	50.0% 13/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Dehydration	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Dermatitis acneiform	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Diarrhoea	96.2% 25/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Dizziness	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Dry mouth	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Dry skin	23.1% 6/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Dysgeusia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Dyspepsia	26.9% 7/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Epistaxis	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
General disorders Fatigue	50.0% 13/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Gastrooesophageal reflux disease	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Headache	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hypercalcaemia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hyperkalaemia	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Vascular disorders Hypertension	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hypokalaemia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hypomagnesaemia	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Metabolism and nutrition disorders Hypophosphataemia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Psychiatric disorders Insomnia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Lethargy	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Investigations Lipase increased	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Mouth ulceration	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
General disorders Mucosal inflammation	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Nausea	65.4% 17/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Paronychia	11.5% 3/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Pruritus	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
General disorders Pyrexia	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Rash	34.6% 9/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Rash erythematous	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Rash maculo-papular	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Rash pruritic	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Skin and subcutaneous tissue disorders Skin ulcer	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Stomatitis	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Nervous system disorders Taste disorder	7.7% 2/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Infections and infestations Urinary tract infection	15.4% 4/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Gastrointestinal disorders Vomiting	34.6% 9/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
Investigations Weight decreased	19.2% 5/26 • TEAEs were adverse events that started from Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months) for Part A and from Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) for Part B (Cycle length, Part A= 30 days and Part B=28 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Publication restrictions are in place

Restriction type: OTHER