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