Metastatic Neoplasm
Conditions
Brief summary
Primary Objectives: * Part 1 * To characterize the safety and tolerability of SAR442720 in combination with pembrolizumab in participants with advanced solid tumors. * To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in participants with solid tumors. * Part 2 * To determine the anti-tumor activity of SAR442720 in combination with pembrolizumab. * Part 3A * To define the MTD and RP2D for the combination of SAR442720 and adagrasib in participants with KRAS G12C NSCLC * To characterize the safety and tolerability of SAR442720 in combination with adagrasib in participants with KRAS G12C NSCLC * Part 3B * To determine the anti-tumor activity of SAR442720 in combination with adagrasib in participants with KRAS G12C NSCLC * Part 4 * To evaluate the impact of food on the PK of SAR442720 when dosed with pembrolizumab. * To evaluate the impact of the formulations (formulation 1 and formulation 2) on the PK of SAR442720 when dosed with pembrolizumab. Secondary Objectives: * Part 1 * To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with SAR442720. * To estimate the anti-tumor effects of SAR442720 with pembrolizumab. * Part 2 * To assess the safety profile of SAR442720 combined with pembrolizumab. * To assess other indicators of anti-tumor activity. * To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with SAR442720. * Part 3A * To characterize the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720. * To estimate the anti-tumor effects of SAR442720 with adagrasib * Part 3B * To assess the safety profile of SAR442720 with adagrasib in participants with KRAS G12C NSCLC. * To assess other indicators of anti-tumor activity. * To assess the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720. * Part 4 * To assess the safety and tolerability of SAR442720 formulations with pembrolizumab * To estimate the anti-tumor effects of SAR442720 with pembrolizumab.
Detailed description
This open label Phase 1 multicenter study was designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SAR442720 in combination with pembrolizumab in participants with solid tumors in Part 1. In Part 2, in the expansion cohort (Cohort A) we assessed the antitumor activity and safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung cancer. In Part 3, we evaluated the safety, MTD, RP2D and antitumor activity of SAR442720 in combination with adagrasib in participants with lung cancer and KRAS G12C mutation. In Part 4, we evaluated the impact of the formulations (formulation 1 and formulation 2) and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. The expected duration of study intervention for participants may vary, based on progression date; median expected duration of study per participant was estimated to be about 10 months in Part 1, Part 3 and Part 4 (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for long term follow-up) and in Part 2 16 months (up to 1 month for screening, a median of 12 months for treatment and a median of 3 months for long term follow up.)
Interventions
DRUGAdagrasib
Pharmaceutical form:Sterile Tablet Route of administration: Oral
DRUGVociprotafib
Pharmaceutical form: Varies Route of administration: Varies
DRUGPembrolizumab
Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion
Sponsors
Revolution Medicines, Inc.
Mirati Therapeutics Inc.
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be ≥ 18 years of age. * Histologically proven diagnosis of advanced solid tumors. * Participants must have one or more of the following molecular aberrations (Part 1): KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations. * Participants must have following molecular aberration (Part 3A and 3B): - KRAS G12C mutation. * At least 1 measurable disease per RECIST 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Woman of childbearing potential must agree to follow contraceptive guidance. * Capable of giving signed informed consent.
Exclusion criteria
* Predicted life expectancy \<3 months. * Primary central nervous system (CNS) tumors. * Symptomatic or impending cord compression. Stable CNS disease was allowed. * History of cerebrovascular stroke or transient ischemic attack within previous 6 months. * Prior solid organ or hematologic transplant. * History or current retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vascular occlusion (RVO), neovascular macular degeneration. * Any clinically significant cardiac disease. * Active, known or suspected autoimmune disease. * History of or current interstitial lung disease or pneumonitis. * Receipt of a live-virus vaccination within 28 days, viral vaccine that do not contain live virus within 7 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. * Known infection with human immunodeficiency virus (HIV), known uncontrolled hepatitis B infection, active tuberculosis, or severe infection requiring parenteral antibiotic treatment. * Inadequate hematologic, hepatic and renal function. * Known second malignancy. * Impairment of gastrointestinal function. * Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol. * History of severe allergic reaction to any of the study intervention components. The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2D1 | Plasma samples were collected at specified timepoints to determine AUClast for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using non-compartmental analysis (NCA) method. |
| Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of IMP up to 30 days after the last dose; approximately 27 weeks | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. |
| Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs) | Cycle 1 (21 days) | Potential DLTs were defined as the AEs that occurred during the first cycle (C) of treatment, considered by the investigator to be related to IMP, unless due to disease progression or to a cause obviously unrelated to IMP: Grade(G)\>= 4 AEs, G3 neutropenia lasting \>7 days or febrile neutropenia; G3 thrombocytopenia with clinically significant bleeding; any G\>=3 immune-related AEs; G3 nonhematologic AEs; G3 aspartate transaminase, alanine transaminase, and/or total bilirubin elevations that persist \>5 days; possible Hy's law case; G3 QT interval corrected using Fridericia's formula prolongation; retinal vein occlusion any grade; toxicity related to IMP leading to 50% or less dose intensity of SAR442720 and/or delay in initiation of C2 dosing of pembrolizumab by \>15 days, in the absence of recovery to baseline or G \<=1 AE. Potential DLT were reviewed by Sponsor and investigators to confirm them as DLTs. |
| Part 2: Percentage of Participants With Objective Response Rate (ORR) | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) determined by investigator per response evaluation criteria in solid tumors (RECIST) version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 millimeter (mm) OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The confidence interval (CI) was estimated using Clopper-Pearson method. |
| Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | From first dose of IMP up to 30 days after the last dose; approximately 7 weeks | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. |
| Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on C1 D1, C1 D15, C2 D1; Pre-dose on C1 D8 and C6 D1; end of treatment (Week 45) | Plasma samples were collected at specified timepoints for pharmacokinetic (PK) analysis. |
| Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1 | Plasma samples were collected at specified timepoints to determine Cmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method. |
| Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1 | Plasma samples were collected at specified timepoints to determine tmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Time to Response (TTR) | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | TTR was defined as the time interval from the administration of first IMP dose to the first documented evidence of PR or CR determined by the Investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR was estimated using Kaplan-Meier method. |
| Part 2: Percentage of Participants With Clinical Benefit Rate | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | Clinical benefit rate was defined as the percentage of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method. |
| Part 2: Percentage of Participants With Disease Control Rate | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | Disease control rate was defined percentage of participants with confirmed CR or PR or SD as determined by the investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method. |
| Part 2: Progression Free Survival (PFS) | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | PFS was defined as the time from the date of first IMP administration to the date of the first documented PD determined by the investigator per RECIST version 1.1 or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. PFS was estimated using Kaplan-Meier method. |
| Part 1: Plasma Concentration of SAR442720 | Pre-dose, 2, 8, hours post-dose on C1 D1 and C2D1; pre-dose C1D8, C1D15, and C6D1; 2 hours C2D2; and end of treatment (Week 22) | Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations. |
| Part 3A: Plasma Concentration of Adagrasib | Pre-dose, 1, 2, 4, 6, 8 post-dose C1D1 and C1D15; pre-dose C1D8 | Plasma samples were collected at specified timepoints for evaluation of adagrasib PK concentrations. It was calculated using NCA method. |
| Part 3A: Percentage of Participants With Objective Response Rate | Tumor assessments performed till end of treatment, approximately 3 weeks | ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method. |
| Part 3A: Duration of Response | Tumor assessments performed till end of treatment, approximately 3 weeks | DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method. |
| Part 3A: Plasma Concentration of SAR442720 | Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post-dose C1D1; pre-dose C1D8; pre-dose, 0.5, 1, 2, 4, 6 post-dose C1D15, and end of treatment (Week 3) | Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations. It was calculated using NCA method. |
| Part 2: Plasma Concentration of SAR442720 | Pre-dose and 2 hours post-dose C1D1 and C2D1; pre-dose on C1D8, C1D15, C6D1; and end of treatment (Week 104) | Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations. |
| Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1 | Serum samples were collected at specified timepoints for evaluation of pembrolizumab PK concentrations. |
| Parts 1 and 4: Percentage of Participants With Objective Response Rate | Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks (Part 1), 46 weeks (Part 4) | ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method. |
| Part 1: Duration of Response (DoR) | Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks | DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive disease progression(PD) or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method. |
| Part 2: Duration of Response | Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks | DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5mm. DoR was estimated using Kaplan-Meier method. |
| Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | From first dose of IMP up to 30 days after the last dose; approximately 111 weeks | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. |
| Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | From first dose of IMP up to 30 days after the last dose; approximately 50 weeks | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. |
Countries
Argentina, Australia, Chile, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
The study was conducted at 20 centers in 7 countries. A total of 95 participants were screened (Part 1: 24; Part 2: 47; Part 3A: 1; Part 4: 23) between 09 June 2020 and 22 December 2022, of which 30 were screen failures.
Pre-assignment details
The study was conducted in 4 parts (Part 1, 2, 3 and 4), Part 3 was divided into Part 3A and 3B, of which Part 3B was not initiated and no participants were enrolled. The study was terminated due to strategic reasons not related to safety.
Participants by arm
| Arm | Count |
|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab Participants were administered SAR442720 140 mg orally BIW on Days 1 and 4 along with pembrolizumab 200 mg via IV infusion Q3W in 21-day cycles until disease progression, unacceptable AEs, or the participant's or investigator's decision to stop the treatment. | 4 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 along with pembrolizumab 200 mg via IV infusion Q3W in 21-day cycles until disease progression, unacceptable AEs, or the participant's or investigator's decision to stop the treatment. | 13 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%) Participants with PD-L1 TPS\>=50% NSCLC were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg Q6W (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment. | 13 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) Participants with PDL1 TPS 1% - 49% NSCLC were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg Q6W (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment. | 19 |
| Part 3A- SAR442720 100mg BIW + Adagrasib Participants were administered SAR442720 100 mg orally BIW on Days 1 and 2 along with adagrasib 400 mg BID in 21-day cycles until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment. | 1 |
| Part 4- SAR442720 200mg + Pembrolizumab Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles (as tablet during the first cycle and as capsule from Cycle 2) along with an IV infusion of pembrolizumab 200 mg Q3W (21-day cycle)or 400 mg Q6W (42-day cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment. | 15 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 5 | 3 | 0 | 2 |
| Overall Study | Other | 0 | 0 | 1 | 3 | 0 | 1 |
| Overall Study | Progressive disease | 4 | 11 | 6 | 11 | 1 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part 4- SAR442720 200mg + Pembrolizumab | Part 3A- SAR442720 100mg BIW + Adagrasib | Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) | Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%) | Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1- SAR442720 140mg BIW + Pembrolizumab |
|---|---|---|---|---|---|---|---|
| Age, Customized 75 years and over | 13 Participants | 0 Participants | 0 Participants | 7 Participants | 5 Participants | 1 Participants | 0 Participants |
| Age, Customized From 18 to 64 years | 34 Participants | 12 Participants | 1 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants |
| Age, Customized From 65 to 74 years | 18 Participants | 3 Participants | 0 Participants | 6 Participants | 3 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 1 Participants | 0 Participants | 5 Participants | 5 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 13 Participants | 1 Participants | 14 Participants | 8 Participants | 9 Participants | 2 Participants |
| Sex: Female, Male Female | 39 Participants | 13 Participants | 0 Participants | 7 Participants | 7 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 26 Participants | 2 Participants | 1 Participants | 12 Participants | 6 Participants | 5 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 6 / 13 | 5 / 13 | 11 / 19 | 0 / 1 | 7 / 15 |
| other Total, other adverse events | 4 / 4 | 13 / 13 | 12 / 13 | 16 / 19 | 1 / 1 | 14 / 15 |
| serious Total, serious adverse events | 0 / 4 | 7 / 13 | 9 / 13 | 11 / 19 | 0 / 1 | 7 / 15 |
Outcome results
Primary
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.
Time frame: From first dose of IMP up to 30 days after the last dose; approximately 27 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 13 Participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 7 Participants |
Primary
Part 2: Percentage of Participants With Objective Response Rate (ORR)
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) determined by investigator per response evaluation criteria in solid tumors (RECIST) version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 millimeter (mm) OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The confidence interval (CI) was estimated using Clopper-Pearson method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Objective Response Rate (ORR) | 23.1 percentage of participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Objective Response Rate (ORR) | 5.3 percentage of participants |
Primary
Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.
Time frame: From first dose of IMP up to 30 days after the last dose; approximately 7 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TEAEs | 1 Participants |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TESAEs | 0 Participants |
Primary
Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules
Plasma samples were collected at specified timepoints to determine AUClast for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using non-compartmental analysis (NCA) method.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2D1
Population: PK evaluable population consisted of participants who completed all of C1 and C2D1 with meal information, full PK, and no dose reduction/missed doses on C1D1, C1D15 and C2D1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules | C1 D1 (Tablet/Fed) | 9410 hour*ng/mL | Standard Deviation 3310 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules | C1 D15 (Tablet/Fasted) | 10800 hour*ng/mL | Standard Deviation 4290 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules | C2D1 (Capsules/Fasted) | 9800 hour*ng/mL | Standard Deviation 3970 |
Primary
Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules
Plasma samples were collected at specified timepoints to determine Cmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1
Population: PK evaluable population consisted of participants who completed all of C1 and C2D1 with meal information, full PK, and no dose reduction/missed doses on C1D1, C1D15 and C2D1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules | C1D1 (Tablet/Fed) | 637 ng/mL | Standard Deviation 220 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules | C1D15 (Tablet/Fasted) | 828 ng/mL | Standard Deviation 310 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules | C2D1 (Capsules/Fasted) | 658 ng/mL | Standard Deviation 326 |
Primary
Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab
Plasma samples were collected at specified timepoints for pharmacokinetic (PK) analysis.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on C1 D1, C1 D15, C2 D1; Pre-dose on C1 D8 and C6 D1; end of treatment (Week 45)
Population: PK population consisted of participants who had at least 1 measurable SAR442720 concentration after the first dose. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose: C1 D1 | 0 nanogram per milliter (ng/mL) | Standard Deviation 0 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 0.5 hours post-dose: C1 D1 | 207 nanogram per milliter (ng/mL) | Standard Deviation 376 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 1 hours post-dose: C1 D1 | 262 nanogram per milliter (ng/mL) | Standard Deviation 323 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 2 hours post-dose: C1 D1 | 342 nanogram per milliter (ng/mL) | Standard Deviation 324 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 4 hours post-dose: C1 D1 | 488 nanogram per milliter (ng/mL) | Standard Deviation 200 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 8 hours post-dose: C1 D1 | 492 nanogram per milliter (ng/mL) | Standard Deviation 220 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 24 hours post-dose: C1 D1 | 272 nanogram per milliter (ng/mL) | Standard Deviation 94.9 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose: C1 D8 | 36.5 nanogram per milliter (ng/mL) | Standard Deviation 23.6 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose: C1 D15 | 8.67 nanogram per milliter (ng/mL) | Standard Deviation 21.6 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 0.5 hours post-dose: C1 D15 | 458 nanogram per milliter (ng/mL) | Standard Deviation 524 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 1 hours post-dose: C1 D15 | 629 nanogram per milliter (ng/mL) | Standard Deviation 615 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 2 hours post-dose: C1 D15 | 757 nanogram per milliter (ng/mL) | Standard Deviation 441 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 4 hours post-dose: C1 D15 | 649 nanogram per milliter (ng/mL) | Standard Deviation 267 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 8 hours post-dose: C1 D15 | 540 nanogram per milliter (ng/mL) | Standard Deviation 226 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 24 hours post-dose: C1 D15 | 342 nanogram per milliter (ng/mL) | Standard Deviation 127 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose: C2 D1 | 7.50 nanogram per milliter (ng/mL) | Standard Deviation 16.7 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 0.5 hours post-dose: C2 D1 | 238 nanogram per milliter (ng/mL) | Standard Deviation 454 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 1 hours post-dose: C2 D1 | 408 nanogram per milliter (ng/mL) | Standard Deviation 414 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 2 hours post-dose: C2 D1 | 557 nanogram per milliter (ng/mL) | Standard Deviation 341 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 4 hours post-dose: C2 D1 | 583 nanogram per milliter (ng/mL) | Standard Deviation 254 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 8 hours post-dose: C2 D1 | 463 nanogram per milliter (ng/mL) | Standard Deviation 168 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | 24 hours post-dose: C2 D1 | 288 nanogram per milliter (ng/mL) | Standard Deviation 118 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | Pre-dose: C6 D1 | 21.3 nanogram per milliter (ng/mL) | Standard Deviation 21.8 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab | End of treatment (Week 45) | 54.3 nanogram per milliter (ng/mL) | Standard Deviation 42.5 |
Primary
Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules
Plasma samples were collected at specified timepoints to determine tmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1
Population: PK evaluable population consisted of participants who completed all of C1 and C2D1 with meal information, full PK, and no dose reduction/missed doses on C1D1, C1D15 and C2D1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules | C1D1 (Tablet/Fed) | 3.75 hour |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules | C1D15 (Tablet/Fasted) | 2.02 hour |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules | C2D1 (Capsules/Fasted) | 3.6 hour |
Primary
Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs)
Potential DLTs were defined as the AEs that occurred during the first cycle (C) of treatment, considered by the investigator to be related to IMP, unless due to disease progression or to a cause obviously unrelated to IMP: Grade(G)\>= 4 AEs, G3 neutropenia lasting \>7 days or febrile neutropenia; G3 thrombocytopenia with clinically significant bleeding; any G\>=3 immune-related AEs; G3 nonhematologic AEs; G3 aspartate transaminase, alanine transaminase, and/or total bilirubin elevations that persist \>5 days; possible Hy's law case; G3 QT interval corrected using Fridericia's formula prolongation; retinal vein occlusion any grade; toxicity related to IMP leading to 50% or less dose intensity of SAR442720 and/or delay in initiation of C2 dosing of pembrolizumab by \>15 days, in the absence of recovery to baseline or G \<=1 AE. Potential DLT were reviewed by Sponsor and investigators to confirm them as DLTs.
Time frame: Cycle 1 (21 days)
Population: DLT evaluable population consisted of participants who took at least 4 of the 6 planned doses of SAR442720 (Part-1 and Part-3A) and 28 of the 42 planned doses of adagrasib (Part-3A) in the first cycle of the treatment and completed the DLT observation period OR participants who had any DLT observed in the DLT observation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Part 1: Duration of Response (DoR)
DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive disease progression(PD) or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method.
Time frame: Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP and with best overall response (BOR) at least PR. Only responders with BOR with at least a PR were included in the analysis.
Secondary
Part 1: Plasma Concentration of SAR442720
Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.
Time frame: Pre-dose, 2, 8, hours post-dose on C1 D1 and C2D1; pre-dose C1D8, C1D15, and C6D1; 2 hours C2D2; and end of treatment (Week 22)
Population: PK population consisted of participants who had at least 1 measurable SAR442720 concentration after the first dose. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C1 D15 | 267 ng/mL | Standard Deviation 328 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D1 | 332 ng/mL | Standard Deviation 208 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 8 hours post-dose: C1 D1 | 327 ng/mL | Standard Deviation 91 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C2 D1 | 29.4 ng/mL | Standard Deviation 5.4 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 2 hours post-dose: C2 D1 | 516 ng/mL | Standard Deviation 145 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 8 hours post-dose: C2 D1 | 413 ng/mL | Standard Deviation 118 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | End of treatment (Week 22) | 39.0 ng/mL | — |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C1 D15 | 37.1 ng/mL | Standard Deviation 25.7 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 2 hours post-dose: C2 D2 | 698 ng/mL | Standard Deviation 350 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C2 D1 | 29.6 ng/mL | Standard Deviation 24.8 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C6 D1 | 75.9 ng/mL | — |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 2 hours post-dose: C2 D1 | 527 ng/mL | Standard Deviation 337 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | End of treatment (Week 22) | 221 ng/mL | Standard Deviation 334 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D1 | 519 ng/mL | Standard Deviation 270 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 8 hours post-dose: C2 D1 | 409 ng/mL | Standard Deviation 205 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | 8 hours post-dose: C1 D1 | 335 ng/mL | Standard Deviation 91 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 1: Plasma Concentration of SAR442720 | Pre-dose: C1 D8 | 42.5 ng/mL | Standard Deviation 50.4 |
Secondary
Part 2: Duration of Response
DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5mm. DoR was estimated using Kaplan-Meier method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP and with BOR at least PR. Only responders with BOR with at least a PR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Duration of Response | NA months |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Duration of Response | 16.59 months |
Secondary
Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.
Time frame: From first dose of IMP up to 30 days after the last dose; approximately 111 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TEAEs | 13 Participants |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TESAEs | 9 Participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TEAEs | 18 Participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TESAEs | 11 Participants |
Secondary
Part 2: Percentage of Participants With Clinical Benefit Rate
Clinical benefit rate was defined as the percentage of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Clinical Benefit Rate | 30.8 percentage of participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Clinical Benefit Rate | 21.1 percentage of participants |
Secondary
Part 2: Percentage of Participants With Disease Control Rate
Disease control rate was defined percentage of participants with confirmed CR or PR or SD as determined by the investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Disease Control Rate | 53.8 percentage of participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Percentage of Participants With Disease Control Rate | 31.6 percentage of participants |
Secondary
Part 2: Plasma Concentration of SAR442720
Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.
Time frame: Pre-dose and 2 hours post-dose C1D1 and C2D1; pre-dose on C1D8, C1D15, C6D1; and end of treatment (Week 104)
Population: PK population consisted of participants who had at least 1 measurable SAR442720 concentration after the first dose. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D1 | 325 ng/mL | Standard Deviation 202 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D8 | 106 ng/mL | Standard Deviation 154 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D15 | 149 ng/mL | Standard Deviation 234 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C2 D1 | 53.3 ng/mL | Standard Deviation 50.8 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | 2 hours post-dose: C2 D1 | 340 ng/mL | Standard Deviation 211 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C6 D1 | 94.9 ng/mL | Standard Deviation 42.8 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | End of treatment (Week 104) | 22.3 ng/mL | Standard Deviation 39 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | End of treatment (Week 104) | 19.0 ng/mL | Standard Deviation 33.3 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C2 D1 | 83.9 ng/mL | Standard Deviation 159 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D1 | 385 ng/mL | Standard Deviation 285 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C6 D1 | 50.1 ng/mL | Standard Deviation 16.8 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D8 | 100 ng/mL | Standard Deviation 172 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | 2 hours post-dose: C2 D1 | 442 ng/mL | Standard Deviation 369 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Plasma Concentration of SAR442720 | Pre-dose: C1 D15 | 85.1 ng/mL | Standard Deviation 81.4 |
Secondary
Part 2: Progression Free Survival (PFS)
PFS was defined as the time from the date of first IMP administration to the date of the first documented PD determined by the investigator per RECIST version 1.1 or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. PFS was estimated using Kaplan-Meier method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Progression Free Survival (PFS) | 3.38 months |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Progression Free Survival (PFS) | 1.95 months |
Secondary
Part 2: Time to Response (TTR)
TTR was defined as the time interval from the administration of first IMP dose to the first documented evidence of PR or CR determined by the Investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR was estimated using Kaplan-Meier method.
Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP and with BOR at least PR. Only responders with BOR with at least a PR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 2: Time to Response (TTR) | 2.23 months |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Part 2: Time to Response (TTR) | 4.34 months |
Secondary
Part 3A: Duration of Response
DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method.
Time frame: Tumor assessments performed till end of treatment, approximately 3 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP and with BOR at least PR. Only responders with BOR with at least a PR were included in the analysis.
Secondary
Part 3A: Percentage of Participants With Objective Response Rate
ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method.
Time frame: Tumor assessments performed till end of treatment, approximately 3 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Percentage of Participants With Objective Response Rate | 0 percentage of participants |
Secondary
Part 3A: Plasma Concentration of Adagrasib
Plasma samples were collected at specified timepoints for evaluation of adagrasib PK concentrations. It was calculated using NCA method.
Time frame: Pre-dose, 1, 2, 4, 6, 8 post-dose C1D1 and C1D15; pre-dose C1D8
Population: PK population consisted of participants who had at least 1 measurable adagrasib concentration after the first dose.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | Pre-dose: C1 D1 | 0 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 1 hours post-dose: C1 D1 | 376 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 2 hours post-dose: C1 D1 | 727 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 4 hours post-dose: C1 D1 | 1560 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 6 hours post-dose: C1 D1 | 1330 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 8 hours post-dose: C1 D1 | 1180 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | Pre-dose: C1 D8 | 2640 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | Pre-dose: C1 D15 | 2110 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 1 hours post-dose: C1 D15 | 2150 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 2 hours post-dose: C1 D15 | 2910 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 4 hours post-dose: C1 D15 | 2880 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 6 hours post-dose: C1 D15 | 2510 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of Adagrasib | 8 hours post-dose: C1 D15 | 2320 ng/mL |
Secondary
Part 3A: Plasma Concentration of SAR442720
Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations. It was calculated using NCA method.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post-dose C1D1; pre-dose C1D8; pre-dose, 0.5, 1, 2, 4, 6 post-dose C1D15, and end of treatment (Week 3)
Population: PK population consisted of participants who had at least 1 measurable SAR442720 concentration after the first dose.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | Pre-dose: C1 D8 | 31.5 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | Pre-dose: C1 D1 | 0 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 0.5 hours post-dose: C1 D1 | 0 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 1 hours post-dose: C1 D1 | 0 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D1 | 170 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 4 hours post-dose: C1 D1 | 432 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 6 hours post-dose: C1 D1 | 356 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 24 hours post-dose: C1 D1 | 167 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | Pre-dose: C1 D15 | 36.6 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 0.5 hours post-dose: C1 D15 | 34.3 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 1 hours post-dose: C1 D15 | 46.6 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 2 hours post-dose: C1 D15 | 306 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 4 hours post-dose: C1 D15 | 376 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | 6 hours post-dose: C1 D15 | 310 ng/mL |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 3A: Plasma Concentration of SAR442720 | End of treatment (Week 3) | 0 ng/mL |
Secondary
Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.
Time frame: From first dose of IMP up to 30 days after the last dose; approximately 50 weeks
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TEAEs | 15 Participants |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events | TESAEs | 7 Participants |
Secondary
Parts 1 and 2: Serum Concentration of Pembrolizumab
Serum samples were collected at specified timepoints for evaluation of pembrolizumab PK concentrations.
Time frame: Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1
Population: PK population consisted of participants who had at least 1 measurable pembrolizumab concentration after the first dose. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Post-dose: C1 D1 | 83200 ng/mL | — |
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C2 D1 | 15500 ng/mL | Standard Deviation 5350 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C6 D1 | 46000 ng/mL | — |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Post-dose: C1 D1 | 63600 ng/mL | Standard Deviation 11600 |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C2 D1 | 14400 ng/mL | Standard Deviation 5480 |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C6 D1 | 23400 ng/mL | Standard Deviation 6450 |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C2 D1 | 10800 ng/mL | Standard Deviation 3520 |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 2: Serum Concentration of Pembrolizumab | Post-dose: C1 D1 | 85200 ng/mL | Standard Deviation 38100 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C6 D1 | 27200 ng/mL | Standard Deviation 6350 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C1 D1 | 0 ng/mL | Standard Deviation 0 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) | Parts 1 and 2: Serum Concentration of Pembrolizumab | Post-dose: C1 D1 | 98900 ng/mL | Standard Deviation 55500 |
| Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) | Parts 1 and 2: Serum Concentration of Pembrolizumab | Pre-dose: C2 D1 | 9290 ng/mL | Standard Deviation 3620 |
Secondary
Parts 1 and 4: Percentage of Participants With Objective Response Rate
ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method.
Time frame: Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks (Part 1), 46 weeks (Part 4)
Population: Safety population consisted of participants who took at least 1 dose of any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1- SAR442720 140mg BIW + Pembrolizumab | Parts 1 and 4: Percentage of Participants With Objective Response Rate | 0 percentage of participants |
| Part 1- SAR442720 200mg BIW + Pembrolizumab | Parts 1 and 4: Percentage of Participants With Objective Response Rate | 0 percentage of participants |
| Part 3A- SAR442720 100mg BIW + Adagrasib | Parts 1 and 4: Percentage of Participants With Objective Response Rate | 6.7 percentage of participants |