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

Abstract

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.

Keywords: Bemarituzumab; FGFR2b; Gastric cancer; Targeted therapy; mFOLFOX6.

Fig. 1

Patient disposition. ^aPatient chose to discontinue treatment but continued in follow-up. ^bRadiographic disease progression was assessed as per RECIST version 1.1. AE, adverse event; mFOLFOX6, modified FOLFOX (infusional 5-fluorouracil, leucovorin, and oxaliplatin); RECIST, Response Evaluation Criteria in Solid Tumors

Fig. 2

PFS and OS in the ITT population. a PFS in the ITT population. b OS in the ITT population. The intention-to-treat population included all patients who underwent randomization. HRs and 95% CIs were calculated using the Cox proportional hazards model, adjusted for randomization stratification factors, including administration of mFOLFOX6 single dose prior to randomization and geographical region. Vertical bars indicate censoring. CI confidence interval; HR hazard ratio; ITT intention-to-treat; mFOLFOX6 modified FOLFOX (infusional 5-fluorouracil, leucovorin, and oxaliplatin); OS overall survival; PFS progression-free survival

Fig. 3

PFS and OS in the FGFR2b ≥ 10% subgroup. a PFS in the FGFR2b ≥ 10% subgroup. b OS in the FGFR2b ≥ 10% subgroup. The FGFR2b ≥ 10% subgroup included patients with FGFR2b tumor staining score of 2 + or 3 + in at least 10% of tumor cells by immunohistochemistry. HRs and 95% CIs were calculated using the unstratified Cox proportional hazards model. Vertical bars indicate censoring. CI confidence interval; FGFR2b IIIb splice isoform of fibroblast growth factor receptor 2; HR hazard ratio; mFOLFOX6 modified FOLFOX (infusional 5-fluorouracil, leucovorin, and oxaliplatin); OS overall survival; PFS progression-free survival