A Study to Evaluate the Safety and the Activity of S095029 as Part of Combination Therapy in Advanced Gastroesophageal Junction/Gastric Cancers.
- Conditions
- MSI-H/dMMR Gastroesophageal-junction CancerMSI-H/dMMR Gastric Cancer
- Interventions
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 32
- 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.
- 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 Adverse Events (AEs) Leading to Dose Discontinuation From screening to 90 days after the last dose Phase 1b and Phase 2
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
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)
A.O.U. Seconda Università Degli Studi Di Napoli
🇮🇹Campania, Italy
Fondazione IRCCS Istituto Nazionale dei Tumor
🇮🇹Milan, Italy
A.O.U. Pisana-Ospedale Santa Chiara
🇮🇹Pisa, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Rome, Italy
Shandong Cancer Hospital Institute
🇨🇳Jinan, Shandong, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
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, Austria
Landeskrankenhaus (SALK)
🇦🇹Salzburg, Austria
Med Universitat Wien-Allgemeines Krankenhaus Der Stadt Wien (AKH)
🇦🇹Wien, Austria
UZ Leuven Campus Gasthuisberg
🇧🇪Leuven, Belgium
Chu de Liege
🇧🇪Liège, Belgium
Cepon - Centro de Pesquisas Oncologicas
🇧🇷Florianópolis, Brazil
Supera Oncologia
🇧🇷Santa Catarina, Brazil
Icesp - Instituto Do Câncer Do Estado de São Paulo
🇧🇷Sao Paulo, Brazil
Instituto Brasileiro de Controle Do Câncer
🇧🇷Sao Paulo, Brazil
Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Mount Sinai Hospital
🇨🇦Toronto, Canada
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Sir Run Run Shaw Hospital Zhejiang University School of Medicine Qingchun Branch
🇨🇳Hangzhou, Zhengjiang Province, China
Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
Institut Bergonié
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Chru Lille - Hopital Claude Huriez
🇫🇷Lille, France
Inst. de Cancer de L'ouest
🇫🇷Saint Herblain, France
Institut Curie
🇫🇷Saint-Cloud, France
Institut de Cancerologie de Lorraine
🇫🇷Vandoeuvre-les-Nancy Cedex, France
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Bekes Megyei Kozponti Korhaz
🇭🇺Gyula, Hungary
Bugat Pal Hospital
🇭🇺Gyöngyös, Hungary
Policlinico G.B. Rossi A.O.U.I. Di Verona
🇮🇹Verona, Italy
Cancer Institute Hospital of Jfcr
🇯🇵Koto-Ku, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chou-ku, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Pan American Center For Oncology Trials, Llc
🇵🇷Rio Piedras, Puerto Rico
University Hospital Vall D'Hebron Institute of Oncology (VHIO)
🇪🇸Barcelona, Spain
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario de Valencia
🇪🇸Valencia, Spain
The Royal Marsden in Chelsea
🇬🇧London, United Kingdom
The Royal Marsden in Sutton
🇬🇧Sutton, Surrey, United Kingdom