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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
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
Institut de Cancérologie de l'Ouest
Angers, France
Institut Bergonié
Bordeaux, France
CHRU de Brest
Brest, France
Centre François Baclesse
Caen, France
Centre Georges François Leclerc
Dijon, France
Centre Léon Bérard
Lyon, France
Institut Paoli Calmette
Marseille, France
CHU de Poitiers
Poitiers, France
CHU de Rennes
Rennes, France
Institut de Cancérologie de l'Ouest
Saint-Herblain, France
...and 2 more locations
The primary objective is to evaluate the efficacy of a combination of FLOT chemotherapy with bemarituzumab as perioperative treatment for gastric and GEJ adenocarcinoma.
The primary endpoint is the complete pathological response in histological result of primary tumour and lymph nodes from the surgical resection, using Becker tumour scale (TG1 to TG3) from TG1 (a and b) to TG2 resection grading
Time frame: 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.