MSI-H/dMMR Gastric Cancer, MSI-H/dMMR Gastroesophageal-junction Cancer
Conditions
Keywords
Anti-NKG2A, S095029, pembrolizumab, MSI-H/dMMR, Gastric cancer, Gastroesophageal-junction cancer
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.
Interventions
DRUGS095029
Participants will be treated with S095029 via intravenous (IV) infusion every 3 weeks (Q3W).
DRUGpembrolizumab 200 mg (KEYTRUDA ®)
Participants will be treated with 200 mg of pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W).
Sponsors
Servier Bio-Innovation LLC
Merck Sharp & Dohme LLC
Institut de Recherches Internationales Servier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| Overall Survival (OS) | Approximately 2 years | Phase 1b and Phase 2. The time from first S095029 dose to death due to any cause. |
| 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). |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Hungary, Italy, Japan, Puerto Rico, Spain, United Kingdom, United States
Outcome results
None listed