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

Phase 1

Recruiting

• Conditions: MSI-H/dMMR Gastroesophageal-junction Cancer; MSI-H/dMMR Gastric Cancer
• Interventions: Drug: S095029; Drug: pembrolizumab 200 mg (KEYTRUDA ®)

• Registration Number: NCT06116136
• Lead Sponsor: Servier Bio-Innovation LLC

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-09-28
• Study First Submitted QC: 2023-10-30
• Study First Posted: 2023-11-03
• Study Start: 2024-08-31
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-09
• Primary Completion: 2026-06-10
• Study Completion: 2029-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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/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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
S095029 and pembrolizumab	pembrolizumab 200 mg (KEYTRUDA ®)	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.
S095029 and pembrolizumab	S095029	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.

Primary Outcome Measures

Name	Time	Method
Number of Dose-Limiting Toxicities (DLTs)	At the end of Cycle 1 (each cycle is 21 days)	Phase 1b and Phase 2
Total Number of Adverse Events (AEs)	From screening to 90 days after the last dose	Phase 1b and Phase 2
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays	From screening to 90 days after the last dose	Phase 1b and Phase 2
Adverse Events (AEs) Leading to Dose Discontinuation	From screening to 90 days after the last dose	Phase 1b and Phase 2
Objective Response Rate (ORR)	Approximately 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	Approximately 2 years	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).
Overall Survival (OS)	Approximately 2 years	Phase 1b and Phase 2. The time from first S095029 dose to death due to any cause.
Progression-Free Survival (PFS)	Approximately 2 years	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).
Disease Control Rate (DCR)	Approximately 2 years	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).
Trough Concentrations of S095029 (Ctrough)	From first dose to 30 days after the last dose	Phase 1b and Phase 2.
Concentration of potential antibodies directed against S095029	From screening to 30 days after the last dose, or end of study if clinically indicated	Phase 1b and Phase 2.
Objective Response Rate (ORR)	Approximately 2 years	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).

Trial Locations

Locations (49)

Ocala Oncology Center Pl; 🇺🇸 Ocala, Florida, United States

Investigative Clinical Research of Indiana, Llc; 🇺🇸 Noblesville, Indiana, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

The Queen Elizabeth Hospital; 🇦🇺 Woodville South, Australia

Ordensklinikum Linz; 🇦🇹 Linz, Upper Austria, Austria

Med Universitat Wien-Allgemeines Krankenhaus Der Stadt Wien (AKH); 🇦🇹 Wien, Vienna, Austria

Landeskrankenhaus (SALK); 🇦🇹 Salzburg, Austria

UZ Leuven Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Chu de Liege; 🇧🇪 Liège, Belgium

Cepon - Centro de Pesquisas Oncologicas; 🇧🇷 Florianópolis, Brazil

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