Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Adagrasib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Part 1:

SAR442720 (also known as RMC-4630) will be administered orally twice a week (BIW) followed by pembrolizumab which is given intravenously (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 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)

Part 3A; SAR442720 and adagrasib will be administered orally on a continuous basis.

Part 3B:

Once SAR442720 dose is confirmed in Part 3A SAR442720 and adagrasib will be administered orally on a continuous basis.

Part 4:

SAR442720 will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)

Pharmaceutical form: Varies Route of administration: Varies

SAR442720

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

Pharmaceutical form:Sterile Tablet Route of administration: Oral

Clinical Sciences & Operations

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.

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.

In Part 3, we will evaluate the safety, MTD, RP2D and antitumor activity of SAR442720 in combination with adagrasib in participants with lung cancer and KRAS G12C mutation.

In Part 4, we will evaluate the impact of the formulations (formulation 1 and formulation 2) and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. 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, Part 3 and Part 4 (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.)

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

A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of SAR442720 in Combination With Other Agents in Participants With Advanced Malignancies

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Part 1:

Incidence, nature, and severity of treatment emergent AEs and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for the combination of SAR442720 and pembrolizumab.

Part 1 and 3A:

Incidence of study drug-related dose-limiting toxicities (DLTs) in Cycle 1.

Part 2 and 3B:

Objective response rate defined as the proportion of participants who have a confirmed CR or partial response (PR) determined by investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Part 3A:

Incidence, nature, and severity of TEAEs and SAEs, graded according to NCI CTCAEv5.0 for the combination of SAR442720 and adagrasib.

Part 1 and Part 4:

Objective response rate of SAR442720 and pembrolizumab in all participants. ORR of combination therapy with SAR442720 and pembrolizumab will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.

Part 1 and Part 2 and 3B:

Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR (complete response) or PR (partial response) to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.

Part 2 and 3B and Part 4:

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.

Part 2 and 3B:

Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of PR or CR determined by the Investigator per RECIST v1.1 (for NSCLC).

Part 2 and 3B:

Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months (determined by the Investigator per RECIST v1.1.

Part 2 and 3B:

Disease control rate (DCR) including confirmed CR or PR or stable disease (SD) as determined by the Investigator per RECIST v1.1.

Part 2 and 3B:

Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by the Investigator as per RECIST v1.1 or death due to any cause, whichever occurs first.

Part 3A:

ORR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.

Part 3:

DOR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies	NCT04418661	Metastatic Neop...	SAR442720 Pembrolizumab Adagrasib	18 Years -	Sanofi
Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies	NCT04418661	Metastatic Neop...	SAR442720 Pembrolizumab Adagrasib	18 Years -	Sanofi

Spots Global Cancer Trial Database for sar442720

Every month we try and update this database with for sar442720 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sar442720

Every month we try and update this database with for sar442720 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sar442720 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.