Trial Outcomes & Findings for Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. (NCT NCT05445843)

NCT ID: NCT05445843

Last Updated: 2025-11-14

Results Overview

Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort A.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 96 participants
• Primary outcome timeframe: Up to approximately 22 months
• Results posted on: 2025-11-14

Participant Flow

The study is conducted globally across 19 countries.

Participant milestones

Measure	Cohort A- PD-L1<1% Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.	Cohort B- PD-L1≥ 1% and STK11 Mutation Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.
Overall Study STARTED	72	23
Overall Study Pharmacokinetic Analysis Set (PAS)	69	23
Overall Study Full Pharmacokinetic Analysis Set (FPAS)	14	9
Overall Study Treatment Ongoing	25	5
Overall Study Discontinued From Treatment and Continued in the Follow-up Period	32	10
Overall Study Discontinued From Treatment and Did Not Enter the Follow-up Period	15	8
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	72	23

Reasons for withdrawal

Measure	Cohort A- PD-L1<1% Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.	Cohort B- PD-L1≥ 1% and STK11 Mutation Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.
Overall Study Death	6	3
Overall Study Subject decision	6	2
Overall Study Adverse Event	2	0
Overall Study Treatment ongoing at the time of the data cut-off date 04NOV2024	25	5
Overall Study Progressive disease	17	9
Overall Study Physician Decision	16	4

Baseline Characteristics

Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.

Baseline characteristics by cohort

Measure	Cohort A- PD-L1<1% n=72 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.	Cohort B- PD-L1≥ 1% and STK11 Mutation n=23 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Total n=95 Participants Total of all reporting groups
Age, Continuous	67.7 Years STANDARD_DEVIATION 7.68 • n=10 Participants	63.7 Years STANDARD_DEVIATION 10.29 • n=10 Participants	66.7 Years STANDARD_DEVIATION 8.50 • n=20 Participants
Sex: Female, Male Female	25 Participants n=10 Participants	5 Participants n=10 Participants	30 Participants n=20 Participants
Sex: Female, Male Male	47 Participants n=10 Participants	18 Participants n=10 Participants	65 Participants n=20 Participants
Race/Ethnicity, Customized White	57 Participants n=10 Participants	13 Participants n=10 Participants	70 Participants n=20 Participants
Race/Ethnicity, Customized Asian	11 Participants n=10 Participants	7 Participants n=10 Participants	18 Participants n=20 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=10 Participants	3 Participants n=10 Participants	7 Participants n=20 Participants

PRIMARY outcome

Timeframe: Up to approximately 22 months

Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned and who received at least one dose of study treatment.

Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort A.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=72 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Overall Response Rate (ORR) as Determined by the Investigator in Cohort A	—	29.2 Percentage (%) of participants Interval 19.0 to 41.1

SECONDARY outcome

Timeframe: Up to approximately 22 months

Population: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned and who received at least one dose of study treatment.

Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort B.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=23 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B	—	21.7 Percentage (%) of participants Interval 7.5 to 43.7

SECONDARY outcome

Timeframe: Up to approximately 59 months

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.

Treatment-emergent Adverse Events (TEAEs) in this study are defined as events that begin after the first dose of study treatment and continue until 30 days after the last dose of study treatment, or events that are present prior to the first dose of treatment and increase in severity based on preferred term within 30 days after the last study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Pharmacokinetic Analysis Set (PAS) - Participants with evaluable values.

JDQ443 concentration data of all participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=22 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=65 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Plasma JDQ443 Concentration in All Participants Cycle 3 Day 1 (predose/0hour)	1090 ng/mL Geometric Coefficient of Variation 178.0	1060 ng/mL Geometric Coefficient of Variation 160.9
Plasma JDQ443 Concentration in All Participants Cycle 5 Day 1 (predose/0hour)	1320 ng/mL Geometric Coefficient of Variation 118.4	1000 ng/mL Geometric Coefficient of Variation 73.6
Plasma JDQ443 Concentration in All Participants Cycle 7 Day 1 (predose/0hour)	1400 ng/mL Geometric Coefficient of Variation 99.4	948 ng/mL Geometric Coefficient of Variation 74.2
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (2 hours)	4700 ng/mL Geometric Coefficient of Variation 81.8	3290 ng/mL Geometric Coefficient of Variation 82.7
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (3 hours)	5540 ng/mL Geometric Coefficient of Variation 41.7	3770 ng/mL Geometric Coefficient of Variation 70.4
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (4 hours)	4330 ng/mL Geometric Coefficient of Variation 54.5	3290 ng/mL Geometric Coefficient of Variation 61.0
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (6 hours)	3600 ng/mL Geometric Coefficient of Variation 59.9	2810 ng/mL Geometric Coefficient of Variation 69.7
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (8 hours)	3120 ng/mL Geometric Coefficient of Variation 55.4	2260 ng/mL Geometric Coefficient of Variation 92.9
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (12 hours)	2380 ng/mL Geometric Coefficient of Variation 72.7	1780 ng/mL Geometric Coefficient of Variation 120.5
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 1 (predose/0hour)	0 ng/mL Geometric Coefficient of Variation 0	0 ng/mL Geometric Coefficient of Variation 0
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 1 (4 hours)	4980 ng/mL Geometric Coefficient of Variation 59.8	3170 ng/mL Geometric Coefficient of Variation 80.8
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 1 (6 hours)	4190 ng/mL Geometric Coefficient of Variation 65.7	2970 ng/mL Geometric Coefficient of Variation 65.6
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (predose/0hour)	1490 ng/mL Geometric Coefficient of Variation 97.5	1580 ng/mL Geometric Coefficient of Variation 96.8
Plasma JDQ443 Concentration in All Participants Cycle 1 Day 15 (1 hour)	3390 ng/mL Geometric Coefficient of Variation 89.3	2440 ng/mL Geometric Coefficient of Variation 102.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Pharmacokinetic Analysis Set (PAS) - Chinese participants with evaluable values.

JDQ443 concentration data of Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=5 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=7 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (12 hours)	2600 ng/mL Geometric Coefficient of Variation 164.4	4290 ng/mL Geometric Coefficient of Variation 53.4
Plasma JDQ443 Concentration in Chinese Participants Cycle 3 Day 1 (predose/0hour)	949 ng/mL Geometric Coefficient of Variation 142.6	1110 ng/mL Geometric Coefficient of Variation 42.4
Plasma JDQ443 Concentration in Chinese Participants Cycle 5 Day 1 (predose/0hour)	1050 ng/mL Geometric Coefficient of Variation 174.6	650 ng/mL Geometric Coefficient of Variation 42.9
Plasma JDQ443 Concentration in Chinese Participants Cycle 7 Day 1 (predose/0hour)	1150 ng/mL Geometric Coefficient of Variation 181.6	1530 ng/mL Geometric Coefficient of Variation 60.9
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 1 (predose/0hour)	0 ng/mL Geometric Coefficient of Variation 0	0 ng/mL Geometric Coefficient of Variation 0
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 1 (4 hours)	2890 ng/mL Geometric Coefficient of Variation 110.9	3480 ng/mL Geometric Coefficient of Variation 41.1
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 1 (6 hours)	2730 ng/mL Geometric Coefficient of Variation 92.7	3220 ng/mL Geometric Coefficient of Variation 26.7
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (predose/0hour)	1410 ng/mL Geometric Coefficient of Variation 113.8	1670 ng/mL Geometric Coefficient of Variation 95.7
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (1 hour)	1470 ng/mL Geometric Coefficient of Variation 249.7	2650 ng/mL Geometric Coefficient of Variation 164.1
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (2 hours)	2330 ng/mL Geometric Coefficient of Variation 252.3	3400 ng/mL Geometric Coefficient of Variation 92.3
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (3 hours)	4120 ng/mL Geometric Coefficient of Variation 92.0	5390 ng/mL Geometric Coefficient of Variation 106.9
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (4 hours)	3130 ng/mL Geometric Coefficient of Variation 95.2	3130 ng/mL Geometric Coefficient of Variation 114.6
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (6 hours)	2670 ng/mL Geometric Coefficient of Variation 97.3	2830 ng/mL Geometric Coefficient of Variation 112.6
Plasma JDQ443 Concentration in Chinese Participants Cycle 1 Day 15 (8 hours)	2630 ng/mL Geometric Coefficient of Variation 133.1	4410 ng/mL Geometric Coefficient of Variation 74.8

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Pharmacokinetic Analysis Set (PAS) - Non-Chinese participants with evaluable values.

JDQ443 concentration data of non-Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=17 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=58 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 1 (predose/0hour)	0 ng/mL Geometric Coefficient of Variation 0	0 ng/mL Geometric Coefficient of Variation 0
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 1 (4 hours)	5760 ng/mL Geometric Coefficient of Variation 34.9	3140 ng/mL Geometric Coefficient of Variation 85.5
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 1 (6 hours)	4840 ng/mL Geometric Coefficient of Variation 49.9	2940 ng/mL Geometric Coefficient of Variation 69.8
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (predose/0hour)	1510 ng/mL Geometric Coefficient of Variation 97.5	1570 ng/mL Geometric Coefficient of Variation 98.1
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (1 hour)	4480 ng/mL Geometric Coefficient of Variation 23.1	2400 ng/mL Geometric Coefficient of Variation 103.1
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (2 hours)	5930 ng/mL Geometric Coefficient of Variation 23.8	3270 ng/mL Geometric Coefficient of Variation 87.4
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (3 hours)	6120 ng/mL Geometric Coefficient of Variation 23.9	3500 ng/mL Geometric Coefficient of Variation 67.2
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (4 hours)	4910 ng/mL Geometric Coefficient of Variation 31.2	3300 ng/mL Geometric Coefficient of Variation 55.9
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (6 hours)	4010 ng/mL Geometric Coefficient of Variation 43.4	2810 ng/mL Geometric Coefficient of Variation 66.2
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (8 hours)	3300 ng/mL Geometric Coefficient of Variation 41.00	1950 ng/mL Geometric Coefficient of Variation 89.4
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 1 Day 15 (12 hours)	2320 ng/mL Geometric Coefficient of Variation 62.3	1460 ng/mL Geometric Coefficient of Variation 116.0
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 3 Day 1 (predose/0hour)	1180 ng/mL Geometric Coefficient of Variation 217.6	1050 ng/mL Geometric Coefficient of Variation 175.9
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 5 Day 1 (predose/0hour)	1550 ng/mL Geometric Coefficient of Variation 90.5	1030 ng/mL Geometric Coefficient of Variation 74.7
Plasma JDQ443 Concentration in Non-Chinese Participants Cycle 7 Day 1 (predose/0hour)	1500 ng/mL Geometric Coefficient of Variation 85.1	917 ng/mL Geometric Coefficient of Variation 74.4

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Cmax was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=14 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Observed Maximum Plasma Concentration (Cmax) of JDQ443 All participants	5160 ng/mL Geometric Coefficient of Variation 52.4	4170 ng/mL Geometric Coefficient of Variation 59.8
Observed Maximum Plasma Concentration (Cmax) of JDQ443 Chinese participants	4320 ng/mL Geometric Coefficient of Variation 103.0	6010 ng/mL Geometric Coefficient of Variation 82.5
Observed Maximum Plasma Concentration (Cmax) of JDQ443 non-Chinese participants	5430 ng/mL Geometric Coefficient of Variation 45.7	3920 ng/mL Geometric Coefficient of Variation 57.5

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Tmax was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=14 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 All participants	3.00 Hours Interval 1.0 to 10.8	2.96 Hours Interval 0.967 to 9.5
Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 Chinese participants	3.61 Hours Interval 3.13 to 4.08	3.58 Hours Interval 3.05 to 4.1
Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 non-Chinese participants	2.98 Hours Interval 1.0 to 10.8	2.61 Hours Interval 0.967 to 9.5

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Tlast was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=14 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 All participants	11.1 Hours Interval 10.0 to 21.0	10.1 Hours Interval 6.0 to 16.9
Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 Chinese participants	11.2 Hours Interval 11.1 to 11.4	11.9 Hours Interval 11.6 to 12.2
Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 non-Chinese participants	11.0 Hours Interval 10.0 to 21.0	10.1 Hours Interval 6.0 to 16.9

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUC∞ was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=2 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=3 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443 All participants	41800 hr*ng/mL Geometric Coefficient of Variation 21.7	33400 hr*ng/mL Geometric Coefficient of Variation 69.0
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443 non-Chinese participants	41800 hr*ng/mL Geometric Coefficient of Variation 21.7	33400 hr*ng/mL Geometric Coefficient of Variation 69.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUClast was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=14 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 All participants	44200 hr*ng/mL Geometric Coefficient of Variation 47.6	29100 hr*ng/mL Geometric Coefficient of Variation 79.3
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 Chinese participants	33500 hr*ng/mL Geometric Coefficient of Variation 137.2	52700 hr*ng/mL Geometric Coefficient of Variation 84.7
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 non-Chinese participants	47900 hr*ng/mL Geometric Coefficient of Variation 25.5	26400 hr*ng/mL Geometric Coefficient of Variation 75.7

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUCτ was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=12 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 All participants	42700 hr*ng/mL Geometric Coefficient of Variation 50.6	34500 hr*ng/mL Geometric Coefficient of Variation 69.4
Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 Chinese participants	35400 hr*ng/mL Geometric Coefficient of Variation 135.1	53500 hr*ng/mL Geometric Coefficient of Variation 79.2
Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 non-Chinese participants	45100 hr*ng/mL Geometric Coefficient of Variation 35.0	31600 hr*ng/mL Geometric Coefficient of Variation 67.4

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Population: Full Pharmacokinetic Analysis Set (FPAS) - Participants with evaluable values.

Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. CL/F was listed and summarized using descriptive statistics.

Outcome measures

Measure	Cohort B- PD-L1≥ 1% and STK11 Mutation n=9 Participants Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.	Cohort A- PD-L1<1% n=12 Participants Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.
Total Body Clearance (CL/F) of JDQ443 in Plasma All participants	4680 mL/hr Geometric Coefficient of Variation 50.6	5800 mL/hr Geometric Coefficient of Variation 69.4
Total Body Clearance (CL/F) of JDQ443 in Plasma Chinese participants	5650 mL/hr Geometric Coefficient of Variation 135.1	3730 mL/hr Geometric Coefficient of Variation 79.2
Total Body Clearance (CL/F) of JDQ443 in Plasma non-Chinese participants	4440 mL/hr Geometric Coefficient of Variation 35.0	6340 mL/hr Geometric Coefficient of Variation 67.4

Adverse Events

Cohort A- PD-L1<1%

Serious events: 29 serious events

Other events: 60 other events

Deaths: 15 deaths

Cohort B- PD-L1≥ 1% and STK11 Mutation

Serious events: 10 serious events

Other events: 21 other events

Deaths: 4 deaths

Serious adverse events

Measure	Cohort A- PD-L1<1% n=72 participants at risk Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.	Cohort B- PD-L1≥ 1% and STK11 Mutation n=23 participants at risk Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.
Gastrointestinal disorders Intestinal ischaemia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Blood and lymphatic system disorders Anaemia	4.2% 3/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Cardiac disorders Pericardial effusion	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Abdominal pain	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Diarrhoea	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Chest pain	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Inflammation	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Pyrexia	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Hepatobiliary disorders Cholecystitis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Hepatobiliary disorders Hepatic cytolysis	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Appendicitis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Infection	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Pneumonia	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Respiratory tract infection	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Sepsis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Injury, poisoning and procedural complications Femur fracture	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Hypercalcaemia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Hyperglycaemia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Bone pain	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Brain oedema	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Intracranial tumour haemorrhage	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Neuralgia	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Seizure	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Syncope	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Psychiatric disorders Panic attack	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Renal and urinary disorders Acute kidney injury	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Renal and urinary disorders Nephrolithiasis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 3/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Productive cough	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Vascular disorders Embolism	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Vascular disorders Jugular vein thrombosis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.

Other adverse events

Measure	Cohort A- PD-L1<1% n=72 participants at risk Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.	Cohort B- PD-L1≥ 1% and STK11 Mutation n=23 participants at risk Participants whose tumors harbored a KRAS G12C mutation, a PD-L1 expression ≥ 1%, and an STK11 co-mutation.
Gastrointestinal disorders Dysphagia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Nausea	25.0% 18/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	21.7% 5/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Vomiting	11.1% 8/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Asthenia	19.4% 14/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	13.0% 3/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Fatigue	18.1% 13/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Renal and urinary disorders Haematuria	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Dyspepsia	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Blood and lymphatic system disorders Anaemia	29.2% 21/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Blood and lymphatic system disorders Neutropenia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Abdominal pain	9.7% 7/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Abdominal pain upper	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Constipation	16.7% 12/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	26.1% 6/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Gastrointestinal disorders Diarrhoea	26.4% 19/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders General physical health deterioration	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	13.0% 3/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Oedema	4.2% 3/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Oedema peripheral	18.1% 13/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	21.7% 5/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
General disorders Pyrexia	11.1% 8/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	13.0% 3/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Pneumonia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Infections and infestations Urinary tract infection	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Alanine aminotransferase increased	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Aspartate aminotransferase increased	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Blood creatinine increased	8.3% 6/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Blood magnesium decreased	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Gamma-glutamyltransferase increased	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Neutrophil count decreased	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations Weight decreased	11.1% 8/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	21.7% 5/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Investigations White blood cell count decreased	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Decreased appetite	15.3% 11/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Metabolism and nutrition disorders Hyponatraemia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Arthralgia	15.3% 11/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Back pain	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Myalgia	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Dizziness	2.8% 2/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Dysgeusia	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Nervous system disorders Headache	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	13.0% 3/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Psychiatric disorders Insomnia	6.9% 5/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 8/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	13.0% 3/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	19.4% 14/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.4% 1/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 4/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Skin and subcutaneous tissue disorders Photosensitivity reaction	8.3% 6/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	4.3% 1/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Skin and subcutaneous tissue disorders Pruritus	9.7% 7/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	0.00% 0/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Skin and subcutaneous tissue disorders Rash	9.7% 7/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	17.4% 4/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.
Vascular disorders Hypotension	4.2% 3/72 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.	8.7% 2/23 • From first dose of study treatment up to the cut-off date for the primary analysis (04-Nov-2024), approximately 22 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER