Safety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Neoplasm
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Adagrasib; Drug: Vociprotafib

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.)

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1019
    • Investigational Site Number : 0320001
  • Buenos Aires, Argentina, 1125
    • Investigational Site Number : 0320002
  • Buenos Aires, Argentina, 1093
    • Investigational Site Number : 0320004
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Investigational Site Number : 0320003
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Investigational Site Number : 0360002
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Investigational Site Number : 0360001
  • Victoria
    • Melbourne, Victoria, Australia, 3084
      • Investigational Site Number : 0360003
• Chile
  • La Araucanía
    • Temuco, La Araucanía, Chile, 4780000
      • Investigational Site Number : 1520002
  • Reg Metropolitana De Santiago
    • Santiago, Reg Metropolitana De Santiago, Chile, 8420383
      • Investigational Site Number : 1520001
  • Valparaíso
    • Viña Del Mar, Valparaíso, Chile, 2520598
      • Investigational Site Number : 1520003
• Korea, Republic of
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
      • Investigational Site Number : 4100003
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
      • Investigational Site Number : 4100002
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03722
      • Investigational Site Number : 4100001
• Spain
  • Madrid, Spain, 28040
    • Investigational Site Number : 7240001
  • Madrid, Spain, 28050
    • Investigational Site Number : 7240002
  • Valencia, Spain, 46010
    • Investigational Site Number : 7240003
• Taiwan
  • Tainan City, Taiwan, 704
    • Investigational Site Number : 1580002
  • Taipei City, Taiwan, 100
    • Investigational Site Number : 1580001
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center- Site Number : 8400002
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center- Site Number : 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1- SAR442720 140 mg BIW + Pembrolizumab; Participants were administered SAR442720 140 milligram (mg) orally twice a week (BIW) on Days 1 and 4 along with pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day cycles until disease progression, unacceptable adverse events (AEs), or the participant's or investigator's decision to stop the treatment.	Drug: Pembrolizumab; Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630
Experimental: 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.	Drug: Pembrolizumab; Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630
Experimental: Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%); Participants with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS)>=50% non-small cell lung cancer (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 once in every 6 weeks (Q6W) (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.	Drug: Pembrolizumab; Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630
Experimental: 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.	Drug: Pembrolizumab; Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630
Experimental: Part 3A- SAR442720 100mg BIW + Adagrasib; Participants were administered SAR442720 100 mg orally BIW on Days 1 and 2 along with adagrasib 400 mg orally twice daily (BID) in 21-day cycles until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.	Drug: Adagrasib; Pharmaceutical form:Sterile Tablet Route of administration: Oral; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630
Experimental: 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.	Drug: Pembrolizumab; Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion; Drug: Vociprotafib; Pharmaceutical form: Varies Route of administration: Varies; Other Names: SAR442720, RMC-4630

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of IMP up to 30 days after the last dose; approximately 27 weeks
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.	Cycle 1 (21 days)
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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	From first dose of IMP up to 30 days after the last dose; approximately 7 weeks
Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab	Plasma samples were collected at specified timepoints for pharmacokinetic (PK) analysis.	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)
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.	Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2D1
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.	Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1
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.	Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Plasma Concentration of SAR442720	Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.	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)
Part 2: Plasma Concentration of SAR442720	Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.	Pre-dose and 2 hours post-dose C1D1 and C2D1; pre-dose on C1D8, C1D15, C6D1; and end of treatment (Week 104)
Parts 1 and 2: Serum Concentration of Pembrolizumab	Serum samples were collected at specified timepoints for evaluation of pembrolizumab PK concentrations.	Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1
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.	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)
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.	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 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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	From first dose of IMP up to 30 days after the last dose; approximately 111 weeks
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.	From first dose of IMP up to 30 days after the last dose; approximately 50 weeks
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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
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.	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)
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.	Pre-dose, 1, 2, 4, 6, 8 post-dose C1D1 and C1D15; pre-dose C1D8
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.	Tumor assessments performed till end of treatment, approximately 3 weeks
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.	Tumor assessments performed till end of treatment, approximately 3 weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Mirati Therapeutics Inc.; Revolution Medicines, Inc.
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• TCD16210 Plain language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2020
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Adagrasib; Pembrolizumab
• Other Study ID Numbers: TCD16210 (Other Identifier: Sanofi Identifier); U1111-1244-2555 (Registry Identifier: ICTRP); 2020-000436-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No