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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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MSI-H/dMMR Gastroesophageal-junction Cancer, MSI-H/dMMR Gastric Cancer

Intervention / Treatment
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* Drug: S095029
* Drug: Pembrolizumab 200 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S095029 and Pembrolizumab<br>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<br>* Participants will be treated with S095029 via intravenous (IV) infusion every 3 weeks (Q3W).<br>Drug: Pembrolizumab 200 mg<br>* Participants will be treated with 200 mg of pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-NKG2A, S095029, Pembrolizumab, MSI-H/dMMR, Gastric cancer, Gastroesophageal-junction cancer