Clinical Trials /

Safety and Efficacy Study of SAR442720 in Combination With Pembrolizumab in Advanced Malignancies

NCT04418661

Description:

Primary Objective: Part 1: - To characterize the safety and tolerability of SAR442720 in combination with pembrolizumab in patients with advanced solid tumors including NSCLC who progressed on anti-PD-1/PD L1 containing therapy and advanced colorectal cancer (CRC) after progression to all standard of care (SOC) therapy. - To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in patients with solid tumors Part 2: - To determine the antitumor activity of SAR442720 in combination with pembrolizumab Secondary Objective: Part 1: - To document the pharmacokinetic (PK) of SAR442720 in combination with pembrolizumab and to document the PK of pembrolizumab in combination with SAR442720 - To estimate the anti-tumor effects of SAR442720 in combination with pembrolizumab in all participants Part 2: - To assess the safety profile of SAR442720 in combination with pembrolizumab - To assess other indicators of antitumor activity. - To assess the pharmacokinetic (PK) of SAR442720 in combination with pembrolizumab, and to assess the PK of pembrolizumab in combination with SAR442720

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of SAR442720 in Combination With Pembrolizumab in Advanced Malignancies
  • Official Title: A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of SAR442720 in Combination With Pembrolizumab in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: TCD16210
  • SECONDARY ID: U1111-1244-2555
  • NCT ID: NCT04418661

Conditions

  • Metastatic Neoplasm

Interventions

DrugSynonymsArms
SAR442720SAR442720
PembrolizumabSAR442720

Purpose

Primary Objective: Part 1: - To characterize the safety and tolerability of SAR442720 in combination with pembrolizumab in patients with advanced solid tumors including NSCLC who progressed on anti-PD-1/PD L1 containing therapy and advanced colorectal cancer (CRC) after progression to all standard of care (SOC) therapy. - To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in patients with solid tumors Part 2: - To determine the antitumor activity of SAR442720 in combination with pembrolizumab Secondary Objective: Part 1: - To document the pharmacokinetic (PK) of SAR442720 in combination with pembrolizumab and to document the PK of pembrolizumab in combination with SAR442720 - To estimate the anti-tumor effects of SAR442720 in combination with pembrolizumab in all participants Part 2: - To assess the safety profile of SAR442720 in combination with pembrolizumab - To assess other indicators of antitumor activity. - To assess the pharmacokinetic (PK) of SAR442720 in combination with pembrolizumab, and to assess the PK of pembrolizumab in combination with SAR442720

Detailed Description

      This open label Phase 1 multicenter study is 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 will assess the antitumor activity and
      safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung
      cancer.

      The expected duration of study intervention for participants may vary, based on progression
      date; median expected duration of study per participant is estimated to be about 10 months in
      Part 1 (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.)
    

Trial Arms

NameTypeDescriptionInterventions
SAR442720ExperimentalPart 1: SAR442720 (also known as RMC-4630) will be administered orally with pembrolizumab which is given by IV once every 3 weeks (Q3W). The dose of SAR442720 will be escalated or de-escalated depending on the emerging safety data of the combination. Part 2: SAR442720 (also known as RMC-4630) will be administered orally with pembrolizumab which is given by IV once every 3 weeks (Q3W) or once every 6 weeks (Q6W). Part 2 will assess the antitumor efficacy and safety of adding SAR442720 to pembrolizumab as 1L NSCLC therapy.
  • SAR442720
  • Pembrolizumab

Eligibility Criteria

        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

          -  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.

          -  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 of planned treatment start

          -  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 is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of study-drug related Dose Limiting Toxicities (DLTs) (Part 1)
Time Frame:21 days
Safety Issue:
Description:Incidence and nature of DLTs assessed as the occurrence of adverse events (AE) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.

Secondary Outcome Measures

Measure:PK of SAR442720 (Part 1)
Time Frame:up to 2 years
Safety Issue:
Description:Plasma concentrations of SAR442720.
Measure:PK of pembrolizumab (Part 1)
Time Frame:up to 2 years
Safety Issue:
Description:Serum concentrations of pembrolizumab.
Measure:Objective response rate (ORR) (Part 1)
Time Frame:up to 2 years
Safety Issue:
Description:Objective response rate (ORR) of SAR442720 and pembrolizumab in all participants. ORR of combination therapy with SAR442720 and pembrolizumab will be based on RECIST v1.1
Measure:Duration of response (DoR) (Part 1)
Time Frame:up to 2 years
Safety Issue:
Description:Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.
Measure:Incidence of study-drug related Dose Limiting Toxicities (DLTs) (Part 2)
Time Frame:up to 2 years
Safety Issue:
Description:Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the NCI CTCAE v5 for the combination of SAR442720 and pembrolizumab

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

July 1, 2021