Clinical Trials /

Safety Study of SAR442720 in Combination With Pembrolizumab in Patients With Advanced Malignancies

NCT04418661

Description:

Primary Objective: - 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 Secondary Objective: - 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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of SAR442720 in Combination With Pembrolizumab in Patients With Advanced Malignancies
  • Official Title: A Phase 1, Open-label, Multicenter, Safety 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 Objectives: - 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 maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for the combination of SAR442720 and pembrolizumab in patients with solid tumors Secondary Objectives: - 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

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.

      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
      (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months
      for long term follow-up).
    

Trial Arms

NameTypeDescriptionInterventions
SAR442720ExperimentalSAR442720 (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.
  • 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: 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)
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
Time Frame:up to 2 years
Safety Issue:
Description:Plasma concentrations of SAR442720.
Measure:PK of pembrolizumab
Time Frame:up to 2 years
Safety Issue:
Description:Serum concentrations of pembrolizumab.
Measure:Objective Response Rate (ORR)
Time Frame:up to 2 years
Safety Issue:
Description:Percentage of participants with a best response of complete response (CR) or partial response (PR) of SAR442720 and pembrolizumab based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measure:Best overall response (BOR)
Time Frame:up to 2 years
Safety Issue:
Description:Percentage of participants with a CR, PR, or stable disease (SD) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Details

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

Last Updated

June 24, 2020