MONEO: A phase II study of avelumab plus FLOT in the peri-operative treatment for patients with resectable gastric or gastroesophageal junction cancer

Background Gastric or gastroesophageal junction cancer (GC) represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well-characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 avelumab (Av) antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy has demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Trial design MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 20th of March 2021, 40 patients have been enrolled, 28 of them have had surgery. Despite the difficulties during the COVID19 pandemic, only two patients had been withdrawn from the study. Clinical trial identification EudraCT 2019-000782-21 ClinicalTrials NCT03979131. Legal entity responsible for the study VHIO Vall d'Hebron Institute of Oncology. Funding Merck. Disclosure A. Vivancos: Advisory / Consultancy: Bayer, Merck, Novartis, Roche (Advisory Board), Bristol Myers Squibb, Guardant Health (Advisory Board), Sysmex (Consultant), Ferrer (Technology Transfer DX Field); Research grant / Funding (institution): Bristol Myers Squibb, Cellestia Biotech, Chittern, Debbio, Novartis, Roche, Sysmex. J. Tabernero: Honoraria (self): educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Advisory / Consultancy: Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. G. Villacampa: Honoraria (Institution): MSD; Advisory / Consultancy: AstraZeneca. I. Melero: Advisory / Consultancy: BMS; Phamamar; F-STAR, Alligator; AstraZeneca; Roche-Genentech; Numab, EMD; Gossamer; Genmab; Research grant / Funding (self): BMS; Roche, AstraZeneca, Genmab; Alligator. All other authors have declared no conflicts of interest.