Abstract 496TiP
Background
FTD/TPI is approved in third-line treatment of patients with aGA/GEJA and first-line treatment is platinum-based chemotherapy +/- immune checkpoint inhibitors. The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile.
Trial design
This phase 2 multicenter randomized study (NCT05476796) is designed to evaluate the efficacy and safety of FTD/TPI + oxaliplatin ± nivolumab in patients with HER2-negative aGA/GEJA, unfit for triplet chemotherapy, in the first-line palliative setting in comparison with FOLFOX ± nivolumab. The randomization (1:1) is stratified by ECOG-PS, age, and PD-L1-CPS score. Main eligibility criteria are age ≥ 18 years, histologically proven aGA/GEJA, no dysphagia or difficulty in swallowing, no prior palliative chemotherapy, no HER2 overexpression/amplification, ECOG-PS 0-2, and adequate organs functions. The tumour has to be measurable (RECIST 1.1). Treatment regimens (14-day cycle) are FTD/TPI 35mg/m2 twice daily on D1-D5 days, oxaliplatin 70mg/m2 IV infusion on D1 of cycle 1 then 85mg/m2 IV from cycle 2 to 8 ± nivolumab 240mg IV infusion on D1 (arm A) versus leucovorin 400 mg/m2 (or 200 mg/m2 if levoleucovorin) + oxaliplatin 85 mg/m2 followed by 5-FU bolus 400 mg/m2 then 5-FU 2400 mg/m2 as a 46-hours continuous IV infusion ± nivolumab 240mg IV infusion on D1 (Arm B). Oxaliplatin will be stopped after 8 cycles in both arms. 5FU or FTD/TPI +/- nivolumab should be continued as maintenance therapy. Treatment will be administered until disease progression or unacceptable toxicity. The primary endpoint is PFS. Secondary endpoints include OS, ORR, safety, time to PS deterioration >2, and quality of life. The sample size calculation is based on an assumption of a gain of 4.1 months in median PFS from 7.7 to 11.8 months (HR=0.65), β=20%, 1-sided α=10%. 118 patients have to be enrolled for a final analysis after 97 events. Planned accrual duration is 3 years, 11 patients have already been enrolled.
Clinical trial identification
NCT05476796.
Legal entity responsible for the study
Unicancer.
Funding
Servier.
Disclosure
C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daichi Sankyo; Financial Interests, Institutional, Invited Speaker: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daichi Sankyo, MSD. V. Jestin: Financial Interests, Personal, Other, invitation à une formation: Novartis, MSD, Merck; Financial Interests, Personal, Other, contribution Organisation Réunion Scientifique: Leo Pharma; Financial Interests, Personal, Invited Speaker: Sanofi. C. Toullec: Financial Interests, Personal, Invited Speaker: Amgen, BMS, MSD, Pierre Fabre, Viatris; Financial Interests, Personal, Advisory Board: Bayer, Sanofi, Servier, AstraZeneca, Oncoscience; Financial Interests, Personal, Expert Testimony: Merck Serono. T. Aparicio: Financial Interests, Personal, Invited Speaker, 2022: Servier; Financial Interests, Personal, Invited Speaker, 3 Conferences: Pierre Fabre; Financial Interests, Personal, Advisory Board, 2 Board in 2022 and 2023: BMS; Financial Interests, Personal, Invited Speaker, 1 conference: MSD; Non-Financial Interests, Leadership Role, 2021-2024: Fédération Francophone de Cancérologie Digestive. M. Ben Abdelghani: Financial Interests, Personal, Invited Speaker: Incyte, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck, BMS, Bayer; Financial Interests, Institutional, Advisory Board: Deciphera. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera, Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. C. Coutzac: Financial Interests, Personal, Advisory Board: BMS, Servier, Pierre Fabre, Merck Serono; Financial Interests, Institutional, Advisory Board: BMS, Amgen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, MSD, ImCore Roche Genentech. O. Dubreuil: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Sanofi, Pierre Fabre, Servier, MSD, AstraZeneca. L. Evesque: Financial Interests, Personal, Advisory Board: Servier, Amgen, MSD, Merck, Astellas. M. Muller: Financial Interests, Institutional, Invited Speaker: Servier. E. Soularue: Financial Interests, Personal, Advisory Board: Amgen; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Prodige. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. D. Botsen: Financial Interests, Personal, Invited Speaker: Accord Healthcare, Amgen, Sanofi, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Role: Accord Healthcare, Amgen, Sanofi, Servier, Pierre Fabre. All other authors have declared no conflicts of interest.