Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 27; no. 3; pp. 558 - 570
• Main Authors: Wainberg, Zev A., Kang, Yoon-Koo, Lee, Keun-Wook, Qin, Shukui, Yamaguchi, Kensei, Kim, In-Ho, Saeed, Anwaar, Oh, Sang Cheul, Li, Jin, Turk, Haci Mehmet, Teixeira, Alexandra, Hitre, Erika, Udrea, Adrian A., Cardellino, Giovanni Gerardo, Sanchez, Raquel Guardeño, Zahlten-Kümeli, Anita, Taylor, Kate, Enzinger, Peter C.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-05-2024; Springer Nature B.V
• Subjects: Abdominal Surgery; Adenocarcinoma; Adenocarcinoma - pathology; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cancer Research; Clinical outcomes; Clinical trials; ErbB-2 protein; Esophageal Neoplasms; Esophagogastric Junction - pathology; Fluorouracil; Gastric cancer; Gastroenterology; Humans; Immunohistochemistry; Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; NCT; NCT03694522; Oncology; Original; Original Article; Patients; Placebo effect; Placebos; Receptor, Fibroblast Growth Factor, Type 2; Stomach Neoplasms - pathology; Surgical Oncology; Survival analysis; Tumor cells; Tumors; FGFR2b; Bemarituzumab; Targeted therapy; Gastric cancer; mFOLFOX6
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-024-01466-w

Background
We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2–negative gastric or gastroesophageal junction cancer (GC).
Methods
Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months.
Results
In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3–13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7–8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49–1.08); median OS (95% CI) was 19.2 (13.6–24.2) and 13.5 (9.3–15.9) months, respectively (HR 0.77; 95% CI 0.52–1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26–0.73); OS: HR 0.52 (95% CI 0.31–0.85). No new safety findings were reported.
Conclusions
In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).
Clinical trial registration
NCT03694522.