Peri-operative Zimberelimab vs Zimberelimab in Comb With Domvanalimab in Resectable Mismatch Repair Deficient/Micro-satellite Unstable Gastric & Gastro-oesophageal Junctional Adenocarcinoma (ZODIAC)
- Conditions
- Locally Advanced Gastric AdenocarcinomaMSI-H/dMMR Gastric CancerMSI-H/dMMR Gastroesophageal-junction Cancer
- Interventions
- Registration Number
- NCT06250036
- Lead Sponsor
- Royal Marsden NHS Foundation Trust
- Brief Summary
A phase II study of peri-operative anti-PD1 (Zimberelimab) +/- anti-TIGIT (Domvanalimab) in resectable mismatch repair deficient (MMRd)/ high micro-satellite instability (MSI-H) gastric/gastro-oesophageal junctional (GOJ) adenocarcinoma (AC)
- Detailed Description
Primary objective The primary objective of the trial is to evaluate the efficacy of zimberelimab +/- domvanalimab as peri-operative treatment in resectable MMRd/MSI-H gastric/GOJ adenoca. A chemotherapy-sparing approach. The primary endpoint is pathological complete response rate at surgery, and to identify which is the most promising experimental arm (zimberelimab alone vs zimberelimab in combination with domvanalimab).
Secondary objectives
* To assess the safety and tolerability of zimberelimab+/- domvanalimab in this disease setting
* To further assess the efficacy of zimberelimab+/- domvanalimab in terms of radiological response rate, R0 resection rate, progression free survival (PFS) and overall survival (OS)
* To evaluate surgical outcomes following treatment with zimberelimab +/- domvanalimab
Translational analyses on tissue and blood biomarkers aimed at identifying those who derive the most benefit from this immunotherapy combination, and those who are non/poor responders.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Single agent zimberelimab Single agent zimberelimab Single agent zimberelimab (PD-1 inhibitor) Q3W Combination zimberelimab + domvanalimab Combination zimberelimab + domvanalimab Combination zimberelimab + domvanalimab (anti-TIGIT) Q3W
- Primary Outcome Measures
Name Time Method Efficacy of zimberelimab +/- domvanalimab in patients with resectable MMRd/MSI-H gastric/GOJ adenocarcinoma who proceed to surgery 5 years Complete pathological response (pCR) rate, to be assessed following surgery by pathological review pCR defined as complete disappearance of tumour cells in the primary tumour surgical specimen and lymph nodes, pCR graded using Mandard TRG grading system
- Secondary Outcome Measures
Name Time Method Efficacy of zimberelimab +/- domvanalimab in patients with resectable MMRd/MSI-H gastric/GOJ adenocarcinoma (all patients treated with study drug(s)) 5 years Clinical complete response rate (cCR), defined as either pCR in patients who have completed surgery, or a complete response on pre-operative imaging in patients who do not have surgery
Assess the safety of zimberelimab+/- domvanalimab with the incidence of TEAEs, SAEs, AEs leading to discontinuation or delays, irAEs, deaths and laboratory abnormalities per CTCAEv5 grade 5 years Incidence of TEAEs, SAEs, AEs leading to discontinuation or delays, irAEs, deaths and laboratory abnormalities per CTCAEv5 grade
Further assess the anti-tumour effect of zimberelimab +/- domvanalimab and any additional benefit of domvanalimab with radiological response, R0 resection rate, and major surgical complications and survival 5 years EFS,OS, Overall response rate (ORR) by RECIST v1.1, R0 resection rate, length of hospital stay, major surgical complications
Trial Locations
- Locations (2)
Ninewells hospital and Medical School
🇬🇧Dundee, United Kingdom
The Royal Marsden NHSFT
🇬🇧London, United Kingdom