MONEO: Phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC)

MONEO was an open-label, non-randomized, multicentric, phase II study that explored the combination of the anti-PD-1 antibody avelumab (Av) plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) chemotherapy in resectable gastric and gastroesophageal junction cancer (GC) patients (pts) (≥cT2 and/or N+).

Eligible pts received pre-operative 4 cycles of Av + FLOT, surgery 4 to 6w afterwards, and 4 more cycles of Av + FLOT followed by Av up to 1 year. The primary end-point was the percentage of pathological complete response (pCR) and the hypothesis was to increment the historical pCR rate (estimated 16%, based on the FLOT4 Trial) with the addition of Av. Secondary end-points included i) pathological regression grade (Becker classification), ii) complete resection rate (R0), iii) disease-free survival (DFS), iv) overall survival (OS), and v) tolerability. Comprehensive biomarker analysis from tissue and blood were designed in the original study, including the analysis of pathological immune response, TCR clonality, immune contexture characterization, and immunodynamic monitoring.

With a data cut-off of February 2023, a total of 40 pts were enrolled in the study (intention-to-treat population [ITT]) with a median follow-up time of 26.2 months. Baseline characteristics were as follows: median age 64y, male 55%, intestinal/diffuse type 38%/45%, GEJ 40% and stage III 52%. As a result of delays in the drug administration due to COVID-19 pandemic, two pts were excluded from the modified ITT [mITT] population (n=38). The pCR rate in the mITT was 21.1% (95%CI 9.6% - 37.3%) with 8/38 achieving a pCR (22 pts had no pCR and 8 did not undergone surgery due to toxicity, disease progression or newly diagnosed tumour). The R0 resection rate was 68%, R1 11%. Regression grades according to Becker’s classification TRG1a, TRG1b, TRG2, and TRG3 were 21%, 8%, 16%, and 37%, respectively. The 24-months OS for the ITT population was 81% (95%CI 69%-96%). Thirty-two pts (80%) experienced G3-4 adverse events (AEs), and 11 (28%) were avelumab-related G3-4 AEs. No fatal outcomes were reported. Analysis of HER2 expression, microsatellite instability (MSI-H), PD-L1 CPS, tumour infiltrating lymphocytes (TIL’s) and circulating cytokines and immune cells is ongoing.

GC patients treated with peri-operative Av plus FLOT chemotherapy showed a modest pCR compared with historical controls, and the combination was relatively safe with no new signals of toxicity. Exploratory analyses considering tumor (HER2, MSI-H, PDL1 CPS, TILs) and blood (cytokines, immune cells) biomarkers are ongoing and will be partially described during the Congress.

EudraCT 2019-000782-21 ClinicalTrials NCT03979131.

The author.

This study has been carried out with the support from Merck, S.L.U.

M. Alsina: Honoraria (self): MSD, BMS, Amgen; Advisory / Consultancy: MSD, BMS, Lilly. G. Villacampa: Advisory / Consultancy: Astrazeneca; Speaker Bureau / Expert testimony: MSD, GSK, Pierre Fabrer. A. Vivancos: Advisory / Consultancy: Bayer, Merck, Novartis, Roche (Advisory Board), Bristol Meyers Squibb, Guardant Health (Advisory Board), Sysmex (Consultant), Ferrer (Technology Transfer DX Field); Research grant / Funding (institution): Bristol Meyers Squibb, Cellestia Biotech, Chittern, Debbio, Novartis, Roche, Sysmex. J. Tabernero: Honoraria (self): educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Advisory / Consultancy: scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiff Oncology, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc and Tolremo Therapeutics; Research grant / Funding (institution): institutional financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK.; Shareholder / Stockholder / Stock options: Oniria Therapeutics. All other authors have declared no conflicts of interest.