A Study to Evaluate the Safety and the Activity of S095029 as Part of Combination Therapy in Advanced Gastroesophageal Junction/Gastric Cancers.

Open Label, Non-randomized, Phase 1b/2 Trial Investigating the Safety, Tolerability, and Antitumor Activity of S095029 (Anti-NKG2A Antibody) as a Part of Combination Therapy in Participants With Locally Advanced and Unresectable or Metastatic MSI-H/dMMR Gastro-esophageal Junction /Gastric Cancer

This study will investigate the safety, tolerability, and antitumor activity of S095029 (anti-NKG2A antibody) in combination with pembrolizumab in in microsatellite instability-high/Defective mismatch repair (MSI-H/dMMR) locally advanced unresectable or metastatic gastric /GEJ adenocarcinomas.

Study Overview

• Status: Not yet recruiting
• Conditions: MSI-H/dMMR Gastroesophageal-junction Cancer; MSI-H/dMMR Gastric Cancer
• Intervention / Treatment: Drug: S095029; Drug: pembrolizumab 200 mg (KEYTRUDA ®)

Detailed Description

This Phase 1b/2 study will be conducted in two parts; a safety lead-in part (Phase 1b) to identify the RP2D of S095029 in combination with pembrolizumab and an expansion part (Phase 2) to evaluate anti-tumor activity and safety in participants with locally advanced unresectable or metastatic MSI-H/dMMR gastric /GEJ adenocarcinomas.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier, Clinical Studies Department; Phone Number: +33 1 55 72 60 00; Email: scientificinformation@servier.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a confirmed diagnosis of locally advanced and unresectable or metastatic gastric or gastro-esophageal junction adenocarcinoma
• Participants' tumor must have an MSI-H or dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment.

Exclusion Criteria:

• Has received more than one previous line of treatment in the locally advanced and unresectable or metastatic setting.
• Has received prior therapy with any checkpoint inhibitor (anti-PD-1, anti-programmed cell death ligand 1 (PDL1), anti-CTLA4).
• Participants who have received prior systemic anti-cancer therapy including investigational agents within 4 weeks (shorter interval, at least 5 half-lives, for kinase inhibitors or other short half-life drugs) prior to first study treatment.
• Prior radiotherapy if completed less than 2 weeks before first study treatment
• Major surgery less than 4 weeks prior to the first study treatment or participants who have not recovered from the side effects of the surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: S095029 and pembrolizumab; Participants diagnosed with gastric cancer (GC) or gastroesophageal junction cancer (GEJ), not previously treated with checkpoint inhibitors (CPIs) may first be enrolled into a Phase 1b safety lead-in part which will be used to identify the recommended Phase 2 dose (RP2D) of S095029 in combination with pembrolizumab. During the Phase 2 part, participants will receive the recommended Phase 2 dose (RP2D) of S095029, along with pembrolizumab.

Drug: S095029; Participants will be treated with S095029 via intravenous (IV) infusion every 3 weeks (Q3W).; Drug: pembrolizumab 200 mg (KEYTRUDA ®); Participants will be treated with 200 mg of pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Dose-Limiting Toxicities (DLTs)	Phase 1b and Phase 2	At the end of Cycle 1 (each cycle is 21 days)
Total Number of Adverse Events (AEs)	Phase 1b and Phase 2	From screening to 90 days after the last dose
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	Phase 1b and Phase 2	From screening to 90 days after the last dose
Adverse Events (AEs) Leading to Dose Discontinuation	Phase 1b and Phase 2	From screening to 90 days after the last dose
Objective Response Rate (ORR)	Phase 2 ONLY. The Proportion of participants who achieve complete response (CR) or partial response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	Phase 1b and Phase 2. The time from the first documentation of complete response (CR) or partial response (PR) until the documented progressive disease (PD) or death, as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST).	Approximately 2 years
Progression-Free Survival (PFS)	Phase 1b and Phase 2. The time from the first dose of S095029 to first documented PD or death due to any cause, whichever occurs first, as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST).	Approximately 2 years
Disease Control Rate (DCR)	Phase 1b and Phase 2. The proportion of participants who achieved stable disease (SD), PR, or CR (based on participant's best response), as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST).	Approximately 2 years
Overall Survival (OS)	Phase 1b and Phase 2. The time from first S095029 dose to death due to any cause.	Approximately 2 years
Trough Concentrations of S095029 (Ctrough)	Phase 1b and Phase 2.	From first dose to 30 days after the last dose
Concentration of potential antibodies directed against S095029	Phase 1b and Phase 2.	From screening to 30 days after the last dose, or end of study if clinically indicated
Objective Response Rate (ORR)	Phase 1b ONLY. The Proportion of participants who achieve complete response (CR) or partial response (PR), as per immune Response Evaluation Criteria in Solid Tumors (iRECIST).	Approximately 2 years

Collaborators and Investigators

• Sponsor: Servier Bio-Innovation LLC
• Collaborators: Merck Sharp & Dohme LLC; Institut de Recherches Internationales Servier

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): June 10, 2026
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 3, 2023

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; pembrolizumab; Gastroesophageal-junction cancer; MSI-H/dMMR; Anti-NKG2A; S095029
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: CL1-95029-002; Keynote E70 (Other Identifier: Merck); 2023-507995-33 (EudraCT Number); MK-3475-E70 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No