A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of SAR442720 in Combination With Other Agents in Participants With Advanced Malignancies

Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

时间窗: 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)

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules

时间窗: 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 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules

时间窗: 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

时间窗: 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.