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Immunomodulating Agents

Single agent zimberelimab (PD-1 inhibitor) Q3W

Single agent zimberelimab

Combination zimberelimab + domvanalimab (TIGIT inhibitor) Q3W

Combination zimberelimab + domvanalimab

Project Manager

Naureen Dr Starling

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)

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.

A UK multicentre, prospective, randomised open label phase II proof of concept study with screen selection design. There will be two cohorts with a 1:1 randomisation

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)

A Randomised Phase II Study of Zimberelimab Anti-PD1 immunOtherapy +/- Domvanalimab Anti-TIGIT Immunotherapy in Resectable Mismatch Repair Deficient Gastric and Gastro-oesophageal Junctional AdenoCarcinoma

Dynamic ctDNA changes, mIF IHC, and assessment of tumour immune environment including PDL1 status, TMB, genomic changes by whole exome sequencing (WES) and RNA sequencing, immune surveillance by TCR sequencing, HRD testing

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

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

Incidence of TEAEs, SAEs, AEs leading to discontinuation or delays, irAEs, deaths and laboratory abnormalities per CTCAEv5 grade

EFS,OS, Overall response rate (ORR) by RECIST v1.1, R0 resection rate, length of hospital stay, major surgical complications

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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)	NCT06250036	Metastatic Esop... Metastatic Gast...	Single agent zi... Combination zim...	18 Years -	Royal Marsden NHS Foundation Trust
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)	NCT06250036	Metastatic Esop... Metastatic Gast...	Single agent zi... Combination zim...	18 Years -	Royal Marsden NHS Foundation Trust

Spots Global Cancer Trial Database for combination zimberelimab + domvanalimab