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
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
Interventions
Drug | Synonyms | Arms |
---|
SAR442720 | | SAR442720 |
Pembrolizumab | | SAR442720 |
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
Name | Type | Description | Interventions |
---|
SAR442720 | Experimental | 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. | |
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