1406P - Interim response evaluation from a phase II study of capecitabine, oxaliplatin, and anti-PD-1 in dMMR esophagogastric cancer (AuspiCiOus trial)

Background

Doublet cytotoxic treatment demonstrates survival benefit over single drug therapies in patients with advanced esophagogastric cancer (EGC). However, reports on the effects of cytotoxic treatment in dMMR tumors range from beneficial to detrimental. Thus, the value of cytotoxic treatment in dMMR tumors is unclear. Here we aim to evaluate the efficacy of Capecitabine and Oxaliplatin (CapOx) followed by retifanlimab in dMMR gastroesophageal cancer.

Methods

AuspiCiOus is a multi-center, open-label, single arm (phase 2) study in patients with dMMR irresectable or metastatic EGC adenocarcinoma (NCT05177133). Patients are treated with CapOx for two 3-weekly cycles, after which treatment is continued with retifanlimab for 4-weekly cycles up to progression or unacceptable toxicity, with a maximum of two years. Tumor response is determined according to (i)RECIST 1.1 after chemotherapy, two cycles of immunotherapy, and every three months thereafter.

Results

In this interim assessment, 19 patients have started treatment with CapOx. Six patients showed a partial response after CapOx treatment, and twelve patients showed a stable disease (see table). Nine out of 12 patients with tumor shrinkage on chemotherapy showed further tumor shrinkage after two cycles of anti-PD-1 (aPD-1). Six patients showed continued response on subsequent aPD-1. However, four patients showed progressive disease before two cycles of retifanlimab were completed. Table: 1406P

PD: Progressive Disease; iUPD: Unconfirmed Progressive Disease; NT: Non-target lesions only

Conclusions

The interim results demonstrated tumor response to CapOx in a substantial number of MSI tumors. However, some MSI tumors have a poor prognosis and show rapid disease progression within three months after start of treatment, despite chemotherapy or checkpoint inhibition.

Clinical trial identification

NCT05177133.

Editorial acknowledgement

Legal entity responsible for the study

Amsterdam UMC.

Funding

Incyte.

Disclosure

S. Derks: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS, Servier; Financial Interests, Institutional, Funding, sponsoring investigator initiated study: Incyte. H.W.M. van Laarhoven: Financial Interests, Institutional, Invited Speaker: Astellas, BeiGene, Benecke, BMS, Daiichi Sankyo, JAAP, Medtlaks, Novartis, Springer, Travel Congress Management BV; Financial Interests, Institutional, Advisory Board: Amphera, Anocca, Astellas, AstraZeneca, BeiGene, Boehringer Ingelheim, Daiichi Sankyo, Dragonfly, MSD, Servier; Financial Interests, Institutional, Other, Advices on protocol development: Myeloid; Financial Interests, Institutional, Other, Selection of articles for Framingham: Framingham; Financial Interests, Institutional, Research Grant, LyRICX study: Servier; Financial Interests, Institutional, Research Grant, TAPESTRY study: Merck; Financial Interests, Institutional, Research Grant, AUSPICIOUS study: Incyte; Financial Interests, Institutional, Research Grant, LOAD study: ORCA; Financial Interests, Institutional, Coordinating PI: Auristone; Financial Interests, Institutional, Local PI, DESTINY-GASTRIC03: AstraZeneca; Non-Financial Interests, Leadership Role, Chair upper GI Faculty: ESMO; Non-Financial Interests, Institutional, Product Samples, For all clinical study mentioned, study medication is provided: See 'research funding'. All other authors have declared no conflicts of interest.