NCT06967987

Study Evaluating the Combination of Bemarituzumab + FLOT Chemotherapy in Perioperative Setting for Resectable Stage cT2-T4a or N+ Gastric and GEJ Adenocarcinoma Overexpressing FGFR2b

Open-label Non-randomized Multicentric Phase 2 Study Evaluating the Combination of Bemarituzumab + FLOT Chemotherapy in Perioperative Setting for Resectable Stage cT2-T4a or N+ Gastric and GEJ Adenocarcinoma Overexpressing FGFR2b

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Institut Cancerologie de l'Ouest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Gastric and gastro-oesophageal junction (GEJ) adenocarcinomas rank as the fifth leading cause of cancer globally. The standard treatment for resectable non-metastatic cT2-T4NX gastric or GEJ adenocarcinoma is perioperative FLOT chemotherapy. In the FLOT4 trial, which included 55% of GEJ and 45% of gastric tumours, the FLOT chemotherapy regimen improved both disease-free survival and overall survival compared to the ECF/ECX regimen. The median overall survival was 50 months, and median disease-free survival was 30 months for the FLOT experimental arm. About 16% of patients achieved a pathological complete regression (TRG1a) in the modified ITT population treated by FLOT. For GEJ adenocarcinoma, the ESOPEC trial has recently demonstrated the superiority of FLOT regimen compared to radiochemotherapy (CROSS regimen) \[ median overall survival 66 months for FLOT regimen vs 37months \[HR 0.7 95% IC (0.53-0.92) p= 0.012\]. Genomic analyses of gastric and GEJ adenocarcinomas conducted by the Cancer Genome Network Atlas have identified four distinct subtypes of tumours based on their gene expression profile. These subtypes include tumours positive for Epstein-Barr virus, microsatellite unstable tumours, genomically stable tumours, and tumours with chromosomal instability. This research has identified oncogenic driver alterations, leading to new targeted therapies and therapeutic strategies. HER2 amplification and MSI status are current targets for targeted therapies with anti-HER2 antibodies and Immune Checkpoint Inhibitors (ICI), respectively. Trials using these therapies in perioperative settings are ongoing with promising preliminary results. However, targeted therapies are not currently available in the non-metastatic setting. The overexpression of Fibroblast Growth Factor Receptor 2 (FGFR2) is a frequent molecular alteration in gastric and GEJ tumours, presenting a potential new therapeutic target. FGFR2b overexpression is associated with poor prognosis and can be detected through pre-screening by immunohistochemistry. Bemarituzumab, a monoclonal antibody specific to the splice-variant FGFR2b, has shown promising results in combination with chemotherapy in phase 2 trials. Based on the frequency of FGFR2b overexpression, the tolerability of combination therapy with chemotherapy, and the need to improve survival rates for gastric and GEJ cancer patients, it is proposed to test the efficacy of the combination of FLOT chemotherapy and bemarituzumab in the perioperative setting for c T2-T4a or N+ gastric or GEJ adenocarcinoma MSS and overexpressing FGFR2b.

Conditions

• Gastric and Gastro-oesophageal Junction (GEJ) Adenocarcinomas
• Overexpression FGFR2b

Interventions

Type	Name	Description
DRUG	Bemarituzumab + Flot regimen	Bemarituzumab (IV administration) over 30 min (+/- 10min) at C1D1 to C8D1 + 15 mg/kg of bodyweight + single additional dose of 7,5 mg/kg at C1D8 \+ FLOT regimen * Fluorouracil for solution for infusion (IV administration) as a continuous IV infusion approximately 24 hours 2600 mg/m² * Leucovorin (folinic acid) solution for infusion (IV administration) over 120 min on the first day, 200 mg/m² * Oxaliplatin concentrate for solution for infusion (IV administration) over 120 min on the first day, 85 mg/m² * Docetaxel concentrated for solution for infusion (IV administration) over 60 min on the first day, 50 mg/m²

Timeline

• Start date: 2026-01-01
• Primary completion: 2026-01-01
• Completion: 2026-01-01
• First posted: 2025-05-13
• Last updated: 2026-01-21

Locations

12 sites across 1 country: France