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

NCT04418661 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: TCD16210U1111-1244-25552020-000436-22
• Study Type: interventional
• Target: 65
• Locations: 7 countries
• Sites: 20

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.

Conditions

Metastatic Neoplasm

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (16)

• 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)

• 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)

• Parts 1 and 2: Serum Concentration of Pembrolizumab

  Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1

• 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)

• 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

Study Arms (6)

Part 1- SAR442720 140 mg BIW + Pembrolizumab

EXPERIMENTAL

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: Vociprotafib; Drug: Pembrolizumab

Part 1- SAR442720 200mg BIW + Pembrolizumab

EXPERIMENTAL

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: Vociprotafib; Drug: Pembrolizumab

Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%)

EXPERIMENTAL

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: Vociprotafib; Drug: Pembrolizumab

Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%)

EXPERIMENTAL

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: Vociprotafib; Drug: Pembrolizumab

Part 3A- SAR442720 100mg BIW + Adagrasib

EXPERIMENTAL

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: Vociprotafib; Drug: Adagrasib

Part 4- SAR442720 200mg + Pembrolizumab

EXPERIMENTAL

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: Vociprotafib; Drug: Pembrolizumab

Interventions

Vociprotafib DRUG

Pharmaceutical form: Varies Route of administration: Varies

Also known as: SAR442720, RMC-4630

Part 1- SAR442720 140 mg BIW + Pembrolizumab; Part 1- SAR442720 200mg BIW + Pembrolizumab; Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%); Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%); Part 3A- SAR442720 100mg BIW + Adagrasib; Part 4- SAR442720 200mg + Pembrolizumab

Pembrolizumab DRUG

Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion

Part 1- SAR442720 140 mg BIW + Pembrolizumab; Part 1- SAR442720 200mg BIW + Pembrolizumab; Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%); Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%); Part 4- SAR442720 200mg + Pembrolizumab

Adagrasib DRUG

Pharmaceutical form:Sterile Tablet Route of administration: Oral

Part 3A- SAR442720 100mg BIW + Adagrasib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Revolution Medicines, Inc.: collaborator
• Mirati Therapeutics Inc.: collaborator

Study Sites (20)

University of California Irvine Medical Center- Site Number : 8400002

Orange, California, 92868, United States

Location

The University of Texas MD Anderson Cancer Center- Site Number : 8400001

Houston, Texas, 77030, United States

Location

Investigational Site Number : 0320003

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, 1019, Argentina

Location

Investigational Site Number : 0320004

Buenos Aires, 1093, Argentina

Location

Investigational Site Number : 0320002

Buenos Aires, 1125, Argentina

Location

Investigational Site Number : 0360002

Sydney, New South Wales, 2031, Australia

Location

Investigational Site Number : 0360001

Woolloongabba, Queensland, 4102, Australia

Location

Investigational Site Number : 0360003

Melbourne, Victoria, 3084, Australia

Location

Investigational Site Number : 1520002

Temuco, La Araucanía, 4780000, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number : 1520003

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Investigational Site Number : 4100002

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Investigational Site Number : 4100003

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 7240001

Madrid, 28040, Spain

Location

Investigational Site Number : 7240002

Madrid, 28050, Spain

Location

Investigational Site Number : 7240003

Valencia, 46010, Spain

Location

Investigational Site Number : 1580002

Tainan, 704, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 100, Taiwan

Location

Related Links

• TCD16210 Plain language Results Summary

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

pembrolizumab; adagrasib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated due to strategic reasons not related to safety.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 5, 2020
• Study Start: June 9, 2020
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: May 29, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

TW (2); AR (4); ES (3); US (2); CL (3); KR (3); AU (3)