Bemarituzumab Added to Chemotherapy Significantly Benefits Survival in FGFR2b-Positive Gastric and GEJ Cancer
Results from the phase 3 FORTITUDE-101 trial show adding bemarituzumab, a first-in-class anti-FGFR2b antibody, to modified FOLFOX6 (mFOLFOX6) significantly improved survival among patients with unresectable, locally advanced or metastatic FGFR2b expressing gastric or gastroesophageal junction (GEJ) cancer.
These findings were presented by Sun Young Rha, MD, PhD, Yonsei University, Seoul, South Korea, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
The trial enrolled 547 patients with FGFR2b-overexpressing (>0% 2+/3+ tumor cell [TC] staining), non-HER2 positive, unresectable, locally advanced or metastatic gastric or GEJ cancer. Patients were randomized 1:1 to receive either 15 mg/kg of bemarituzumab once every 2 weeks (with a 7.5 mg/kg loading dose on cycle 1 day 8) plus mFOLFOX6 (n = 274) or placebo plus mFOLFOX6 (n = 273).
The primary end point was overall survival (OS) in patients with FGFR2b ≥10% 2+/3+ tumor staining. Key secondary end points included progression-free survival (PFS), objective response rate (ORR) in FGFR2b ≥10% patients, and safety. The FGFR2b ≥10% patient subset was 159 of 274 patients in bemarituzumab arm and 165 of 273 in placebo arm.
OS efficacy boundaries were crossed and full alpha spent at the interim analysis (data cutoff December 9, 2024), so it serves as the primary analysis. A descriptive follow-up analysis was performed at data cutoff (June 20, 2025).
At primary analysis (median follow-up 11.8 months), median OS in FGFR2b ≥10% patients was 17.9 months in the bemarituzumab arm and 12.5 months in the placebo arm (hazard ratio [HR] 0.61; 95% confidence interval [CI], 0.43 to 0.86; P = .005). Median PFS was 8.6 months and 6.7 months, respectively (HR, 0.71; 95% CI, 0.53 to 0.95; P = .019).
At the descriptive follow-up analysis, median OS was 14.5 months in the bemarituzumab arm and 13.2 months in the placebo arm (HR, 0.82; 95% CI, 0.62 to 1.08).
Grade ≥3 treatment-emergent adverse events occurred in 89.5% of patients in the bemarituzumab arm and 78.7% of patients in the placebo arm and grade ≥3 treatment-related adverse events occurred in 60% and 18.4% of patients, respectively.
As Dr Rha concluded, “Results from this trial and upcoming FORTITUDE-102 will further characterize the benefit of [bemarituzumab] in gastric or GEJ [cancer].”
Source:
Rha SY, Pazo Cid RA, Fernandez Montes A, et al. Bemarituzumab (BEMA) plus chemotherapy for advanced or metastatic FGFR2b-overexpressing gastric or gastroesophageal junction cancer (G/GEJC): FORTITUDE-101 phase III study results. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA10
