Peri-operative Zimberelimab (Anti-PD-1) vs Zimberelimab in Combination With Domvanalimab (Anti-TIGIT) in Resectable Mismatch Repair Deficient/Micro-satellite Unstable Gastric and Gastro-oesophageal Junctional Adenocarcinoma (ZODIAC)

Phase 2

Not yet recruiting

• Conditions: Metastatic Esophageal Cancer; Metastatic Gastric Cancer
• Interventions: Drug: Single agent zimberelimab; Drug: Combination zimberelimab + domvanalimab

• 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 preoperative treatment in improving the pathological complete response (pCR) rate as compared to standard FLOT chemotherapy in resectable dMMR/MSI-H gastric/GOJ AC and to identify the most promising experimental arm.

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.

Study Timeline

• Study First Submitted: 2023-12-11
• Status Verified: 2024-01
• Study First Submitted QC: 2024-01-31
• Last Update Submitted: 2024-01-31
• Study First Posted: 2024-02-08
• Last Update Posted: 2024-02-08
• Study Start: 2024-04-01
• Primary Completion: 2026-09-01
• Study Completion: 2031-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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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

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