Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation
Conditions
Keywords
Lung cancer, NSCLC, KRAS G12C, STK11, PD-L1, JDQ443
Brief summary
This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression \< 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).
Detailed description
This is a non-randomized, open-label, single-arm, multicenter, phase II study evaluating the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic KRAS G12C-mutated NSCLC. The study will have 2 non-comparative cohorts that will recruit participants in parallel according to the following characteristics: * Cohort A: participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status. * Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation. The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. One treatment cycle consists of 21 (±3) days. Study completion is defined as the earliest occurrence of one of the following: * The last participant completes last study visit (and the assessments associated with this visit have been documented and followed-up appropriately by the Investigator), dies, withdraws consent, or is lost to follow-up, whichever comes first.\] * In the event of an early study termination decision, the date of that decision. * Another clinical study becomes available that can continue to provide JDQ443 to study participants and all participants with ongoing treatment are transferred to that clinical study.
Interventions
DRUGJDQ443
JDQ443 per os (PO) 200 mg twice a day continuously
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria * Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation or surgical resection with curative intent) or metastatic (stage IV) NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or locally advanced disease are accepted if the time between therapy completion and enrollment is \> 12 months. * Presence of a KRAS G12C mutation (all participants) and: * Cohort A: PD-L1 expression \< 1%, regardless of STK11 mutation status * Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation * At least one measurable lesion per RECIST 1.1. * ECOG performance status ≤ 1. * Participants capable of swallowing study medication. Key
Exclusion criteria
* Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other known druggable alterations will be excluded, if required by local guidelines * Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic NSCLC. * A medical condition that results in increased photosensitivity (i.e., solar urticaria, lupus erythematosus, etc.). * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study. Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Determined by the Investigator in Cohort A | Up to approximately 22 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B | Up to approximately 22 months | 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. |
| Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria | 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. |
| Plasma JDQ443 Concentration in All Participants | 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. | JDQ443 concentration data of all participants were reported separately for each of the two cohorts and summarized using descriptive statistics. |
| Plasma JDQ443 Concentration in Chinese Participants | 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. | JDQ443 concentration data of Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics. |
| Plasma JDQ443 Concentration in Non-Chinese Participants | 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. | JDQ443 concentration data of non-Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics. |
| Observed Maximum Plasma Concentration (Cmax) of JDQ443 | 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. | 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. |
| Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | 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. | 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. |
| Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | 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. | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443 | 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. | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 | 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. | 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. |
| Total Body Clearance (CL/F) of JDQ443 in Plasma | 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. | 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. |
| Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 | 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. | 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. |
Countries
Argentina, Austria, Belgium, Brazil, China, France, Germany, Greece, Hungary, India, Italy, Malaysia, Netherlands, Portugal, Spain, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Recruitment details
The study is conducted globally across 19 countries.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A- PD-L1<1% Participants whose tumors harbored a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status. | 72 |
| 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. | 23 |
| Total | 95 |
Baseline characteristics
| Characteristic | Cohort B- PD-L1≥ 1% and STK11 Mutation | Total | Cohort A- PD-L1<1% |
|---|---|---|---|
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 10.29 | 66.7 Years STANDARD_DEVIATION 8.5 | 67.7 Years STANDARD_DEVIATION 7.68 |
| Race/Ethnicity, Customized Asian | 7 Participants | 18 Participants | 11 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 70 Participants | 57 Participants |
| Sex: Female, Male Female | 5 Participants | 30 Participants | 25 Participants |
| Sex: Female, Male Male | 18 Participants | 65 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 72 | 4 / 23 |
| other Total, other adverse events | 60 / 72 | 21 / 23 |
| serious Total, serious adverse events | 29 / 72 | 10 / 23 |
Outcome results
Primary
Overall Response Rate (ORR) as Determined by the Investigator in Cohort A
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A- PD-L1<1% | Overall Response Rate (ORR) as Determined by the Investigator in Cohort A | 29.2 Percentage (%) of participants |
Secondary
Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 | All participants | 34500 hr*ng/mL | Geometric Coefficient of Variation 69.4 |
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 | Chinese participants | 53500 hr*ng/mL | Geometric Coefficient of Variation 79.2 |
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443 | non-Chinese participants | 31600 hr*ng/mL | Geometric Coefficient of Variation 67.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443 | All participants | 33400 hr*ng/mL | Geometric Coefficient of Variation 69 |
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443 | non-Chinese participants | 33400 hr*ng/mL | Geometric Coefficient of Variation 69 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 | All participants | 29100 hr*ng/mL | Geometric Coefficient of Variation 79.3 |
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 | Chinese participants | 52700 hr*ng/mL | Geometric Coefficient of Variation 84.7 |
| Cohort A- PD-L1<1% | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443 | non-Chinese participants | 26400 hr*ng/mL | Geometric Coefficient of Variation 75.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 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 |
Secondary
Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A- PD-L1<1% | Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B | 21.7 Percentage (%) of participants |
Secondary
Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
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.
Time frame: Up to approximately 59 months
Secondary
Observed Maximum Plasma Concentration (Cmax) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | All participants | 4170 ng/mL | Geometric Coefficient of Variation 59.8 |
| Cohort A- PD-L1<1% | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | Chinese participants | 6010 ng/mL | Geometric Coefficient of Variation 82.5 |
| Cohort A- PD-L1<1% | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | non-Chinese participants | 3920 ng/mL | Geometric Coefficient of Variation 57.5 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | non-Chinese participants | 5430 ng/mL | Geometric Coefficient of Variation 45.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | All participants | 5160 ng/mL | Geometric Coefficient of Variation 52.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Observed Maximum Plasma Concentration (Cmax) of JDQ443 | Chinese participants | 4320 ng/mL | Geometric Coefficient of Variation 103 |
Secondary
Plasma JDQ443 Concentration in All Participants
JDQ443 concentration data of all participants were reported separately for each of the two cohorts and summarized using descriptive statistics.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (4 hours) | 3170 ng/mL | Geometric Coefficient of Variation 80.8 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (6 hours) | 2970 ng/mL | Geometric Coefficient of Variation 65.6 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (predose/0hour) | 1580 ng/mL | Geometric Coefficient of Variation 96.8 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (1 hour) | 2440 ng/mL | Geometric Coefficient of Variation 102 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (2 hours) | 3290 ng/mL | Geometric Coefficient of Variation 82.7 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (3 hours) | 3770 ng/mL | Geometric Coefficient of Variation 70.4 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (4 hours) | 3290 ng/mL | Geometric Coefficient of Variation 61 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (6 hours) | 2810 ng/mL | Geometric Coefficient of Variation 69.7 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (8 hours) | 2260 ng/mL | Geometric Coefficient of Variation 92.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (12 hours) | 1780 ng/mL | Geometric Coefficient of Variation 120.5 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 3 Day 1 (predose/0hour) | 1060 ng/mL | Geometric Coefficient of Variation 160.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 5 Day 1 (predose/0hour) | 1000 ng/mL | Geometric Coefficient of Variation 73.6 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in All Participants | Cycle 7 Day 1 (predose/0hour) | 948 ng/mL | Geometric Coefficient of Variation 74.2 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (12 hours) | 2380 ng/mL | Geometric Coefficient of Variation 72.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (4 hours) | 4330 ng/mL | Geometric Coefficient of Variation 54.5 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (4 hours) | 4980 ng/mL | Geometric Coefficient of Variation 59.8 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 5 Day 1 (predose/0hour) | 1320 ng/mL | Geometric Coefficient of Variation 118.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 1 (6 hours) | 4190 ng/mL | Geometric Coefficient of Variation 65.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (6 hours) | 3600 ng/mL | Geometric Coefficient of Variation 59.9 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (predose/0hour) | 1490 ng/mL | Geometric Coefficient of Variation 97.5 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 3 Day 1 (predose/0hour) | 1090 ng/mL | Geometric Coefficient of Variation 178 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (1 hour) | 3390 ng/mL | Geometric Coefficient of Variation 89.3 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (8 hours) | 3120 ng/mL | Geometric Coefficient of Variation 55.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (2 hours) | 4700 ng/mL | Geometric Coefficient of Variation 81.8 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 7 Day 1 (predose/0hour) | 1400 ng/mL | Geometric Coefficient of Variation 99.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in All Participants | Cycle 1 Day 15 (3 hours) | 5540 ng/mL | Geometric Coefficient of Variation 41.7 |
Secondary
Plasma JDQ443 Concentration in Chinese Participants
JDQ443 concentration data of Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (4 hours) | 3480 ng/mL | Geometric Coefficient of Variation 41.1 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (6 hours) | 3220 ng/mL | Geometric Coefficient of Variation 26.7 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (predose/0hour) | 1670 ng/mL | Geometric Coefficient of Variation 95.7 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (1 hour) | 2650 ng/mL | Geometric Coefficient of Variation 164.1 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (2 hours) | 3400 ng/mL | Geometric Coefficient of Variation 92.3 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (3 hours) | 5390 ng/mL | Geometric Coefficient of Variation 106.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (4 hours) | 3130 ng/mL | Geometric Coefficient of Variation 114.6 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (6 hours) | 2830 ng/mL | Geometric Coefficient of Variation 112.6 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (8 hours) | 4410 ng/mL | Geometric Coefficient of Variation 74.8 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (12 hours) | 4290 ng/mL | Geometric Coefficient of Variation 53.4 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 3 Day 1 (predose/0hour) | 1110 ng/mL | Geometric Coefficient of Variation 42.4 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 5 Day 1 (predose/0hour) | 650 ng/mL | Geometric Coefficient of Variation 42.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Chinese Participants | Cycle 7 Day 1 (predose/0hour) | 1530 ng/mL | Geometric Coefficient of Variation 60.9 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (12 hours) | 2600 ng/mL | Geometric Coefficient of Variation 164.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (4 hours) | 3130 ng/mL | Geometric Coefficient of Variation 95.2 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (4 hours) | 2890 ng/mL | Geometric Coefficient of Variation 110.9 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 5 Day 1 (predose/0hour) | 1050 ng/mL | Geometric Coefficient of Variation 174.6 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 1 (6 hours) | 2730 ng/mL | Geometric Coefficient of Variation 92.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (6 hours) | 2670 ng/mL | Geometric Coefficient of Variation 97.3 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (predose/0hour) | 1410 ng/mL | Geometric Coefficient of Variation 113.8 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 3 Day 1 (predose/0hour) | 949 ng/mL | Geometric Coefficient of Variation 142.6 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (1 hour) | 1470 ng/mL | Geometric Coefficient of Variation 249.7 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (8 hours) | 2630 ng/mL | Geometric Coefficient of Variation 133.1 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (2 hours) | 2330 ng/mL | Geometric Coefficient of Variation 252.3 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 7 Day 1 (predose/0hour) | 1150 ng/mL | Geometric Coefficient of Variation 181.6 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Chinese Participants | Cycle 1 Day 15 (3 hours) | 4120 ng/mL | Geometric Coefficient of Variation 92 |
Secondary
Plasma JDQ443 Concentration in Non-Chinese Participants
JDQ443 concentration data of non-Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (4 hours) | 3140 ng/mL | Geometric Coefficient of Variation 85.5 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (6 hours) | 2940 ng/mL | Geometric Coefficient of Variation 69.8 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (predose/0hour) | 1570 ng/mL | Geometric Coefficient of Variation 98.1 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (1 hour) | 2400 ng/mL | Geometric Coefficient of Variation 103.1 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (2 hours) | 3270 ng/mL | Geometric Coefficient of Variation 87.4 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (3 hours) | 3500 ng/mL | Geometric Coefficient of Variation 67.2 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (4 hours) | 3300 ng/mL | Geometric Coefficient of Variation 55.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (6 hours) | 2810 ng/mL | Geometric Coefficient of Variation 66.2 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (8 hours) | 1950 ng/mL | Geometric Coefficient of Variation 89.4 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (12 hours) | 1460 ng/mL | Geometric Coefficient of Variation 116 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 3 Day 1 (predose/0hour) | 1050 ng/mL | Geometric Coefficient of Variation 175.9 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 5 Day 1 (predose/0hour) | 1030 ng/mL | Geometric Coefficient of Variation 74.7 |
| Cohort A- PD-L1<1% | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 7 Day 1 (predose/0hour) | 917 ng/mL | Geometric Coefficient of Variation 74.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (12 hours) | 2320 ng/mL | Geometric Coefficient of Variation 62.3 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (predose/0hour) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (4 hours) | 4910 ng/mL | Geometric Coefficient of Variation 31.2 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (4 hours) | 5760 ng/mL | Geometric Coefficient of Variation 34.9 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 5 Day 1 (predose/0hour) | 1550 ng/mL | Geometric Coefficient of Variation 90.5 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 1 (6 hours) | 4840 ng/mL | Geometric Coefficient of Variation 49.9 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (6 hours) | 4010 ng/mL | Geometric Coefficient of Variation 43.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (predose/0hour) | 1510 ng/mL | Geometric Coefficient of Variation 97.5 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 3 Day 1 (predose/0hour) | 1180 ng/mL | Geometric Coefficient of Variation 217.6 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (1 hour) | 4480 ng/mL | Geometric Coefficient of Variation 23.1 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (8 hours) | 3300 ng/mL | Geometric Coefficient of Variation 41 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (2 hours) | 5930 ng/mL | Geometric Coefficient of Variation 23.8 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 7 Day 1 (predose/0hour) | 1500 ng/mL | Geometric Coefficient of Variation 85.1 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Plasma JDQ443 Concentration in Non-Chinese Participants | Cycle 1 Day 15 (3 hours) | 6120 ng/mL | Geometric Coefficient of Variation 23.9 |
Secondary
Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A- PD-L1<1% | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | All participants | 10.1 Hours |
| Cohort A- PD-L1<1% | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | Chinese participants | 11.9 Hours |
| Cohort A- PD-L1<1% | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | non-Chinese participants | 10.1 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | All participants | 11.1 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | Chinese participants | 11.2 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443 | non-Chinese participants | 11.0 Hours |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A- PD-L1<1% | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | All participants | 2.96 Hours |
| Cohort A- PD-L1<1% | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | Chinese participants | 3.58 Hours |
| Cohort A- PD-L1<1% | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | non-Chinese participants | 2.61 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | All participants | 3.00 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | Chinese participants | 3.61 Hours |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443 | non-Chinese participants | 2.98 Hours |
Secondary
Total Body Clearance (CL/F) of JDQ443 in Plasma
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A- PD-L1<1% | Total Body Clearance (CL/F) of JDQ443 in Plasma | All participants | 5800 mL/hr | Geometric Coefficient of Variation 69.4 |
| Cohort A- PD-L1<1% | Total Body Clearance (CL/F) of JDQ443 in Plasma | Chinese participants | 3730 mL/hr | Geometric Coefficient of Variation 79.2 |
| Cohort A- PD-L1<1% | Total Body Clearance (CL/F) of JDQ443 in Plasma | non-Chinese participants | 6340 mL/hr | Geometric Coefficient of Variation 67.4 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Total Body Clearance (CL/F) of JDQ443 in Plasma | All participants | 4680 mL/hr | Geometric Coefficient of Variation 50.6 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Total Body Clearance (CL/F) of JDQ443 in Plasma | Chinese participants | 5650 mL/hr | Geometric Coefficient of Variation 135.1 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | Total Body Clearance (CL/F) of JDQ443 in Plasma | non-Chinese participants | 4440 mL/hr | Geometric Coefficient of Variation 35 |