Bemarituzumab extends survival in FGFR2b-overexpressing gastric cancer

The use of bemarituzumab in combination with chemotherapy provides statistically significant survival benefits among patients with advanced or metastatic FGFR2b-overexpressing gastric or gastroesophageal junction cancer (G/GEJC) in the primary analysis of the phase III FORTITUDE-101 trial.

However, after a longer follow-up, the treatment effect of this combination therapy is attenuated at a descriptive analysis.

Bemarituzumab is a first-in-class anti-FGFR2b antibody that “blocks oncogenic signalling through FGFR2b and engages antibody-dependent cell-mediated cytotoxicity,” according to lead author Dr Sun Young Rha, director of the Songdang Institute for Cancer Research at the Yonsei University College of Medicine in Seoul, South Korea. [ESMO 2025, abstract LBA10]

“The FORTITUDE-101 trial met its primary endpoint of overall survival (OS) and key secondary endpoint of progression-free survival (PFS) in patients with FGFR2b-overexpressing G/GEJC, establishing FGFR2b as a validated therapeutic target in this population,” Rha said. [https://oncodaily.com/oncolibrary/fortitude-101-bema-gastric-cancer]

A total of 547 patients with FGFR2b-overexpressing (>0 percent 2+/3+ tumour cell [TC] staining), non-HER2 positive, unresectable, locally advanced or metastatic G/GEJC (median age 62.0 years, 68.7 percent male) were included in this trial.

Rha and colleagues randomized the participants to bemarituzumab (15 mg/kgQ2W + 7.5 mg/kg on cycle 1 day 8) plus mFOLFOX6 (n=274) or matched placebo plus mFOLFOX6 (n=273). OS in patients with FGFR2b ≥10 percent 2+/3+ TC staining was the primary outcome. Secondary outcomes included PFS and objective response rate (ORR), as well as safety.

“Since OS efficacy boundaries were crossed and full alpha spent at the interim analysis (data cutoff 9 December 2024), it serves as the primary analysis,” Rha said. “A descriptive follow-up analysis was performed at data cutoff on 20 June 2025.”

Survival benefit

Of the participants, 159 in the bemarituzumab and 165 in the placebo arm were included in the FGFR2b ≥10 percent patient subset.

The primary analysis (median follow-up 11.8 months) showed that bemarituzumab significantly improved OS in FGFR2b ≥10 percent patients compared with placebo (median 17.9 vs 12.5 months; hazard ratio [HR], 0.61, 95 percent CI, 0.43‒0.86; p=0.005).

At the follow-up analysis (median follow-up 19.4 months), the median OS was 14.5 months (95 percent Ci, 13.0‒17.9) among patients treated with bemarituzumab vs 13.2 percent (95 percent CI, 10.9‒14.7) among those who received placebo (HR, 0.82, 95 percent CI, 0.62‒1.08).

Further analysis revealed improvements in PFS, but not ORR, with bemarituzumab plus chemotherapy. At a median follow-up of 11.1 months, the median PFS was 8.6 months (95 percent CI, 7.5‒9.5) in the bemarituzumab arm vs 6.7 months (95 percent CI, 5.6‒7.6) in the placebo arm (HR, 0.71, 95 percent CI, 0.53‒0.95; p=0.019).

The ORRs were 45.9 percent (95 percent CI, 38.0‒54.0) with bemarituzumab and 44.8 percent (95 percent CI, 37.1‒52.8) with placebo (p=0.90). The median duration of response in the respective arms was 7.0 months (95 percent CI, 5.3‒7.3) and 5.8 months (95 percent CI, 5.0‒7.3).

Safety profile

The rates of any-grade treatment-emergent adverse events (TEAEs) were comparable between the two treatment arms (99 percent vs 98 percent), while grade ≥3 TEAEs were higher with bemarituzumab (90 percent vs 79 percent).

Moreover, any-grade treatment-related adverse events (TRAEs) occurred in 89 percent of patients on bemarituzumab and 66 percent of those on placebo. Grade ≥3 TRAEs were significantly higher in the bemarituzumab arm (60 percent vs 18 percent).

The most common any-grade TEAEs among patients treated with bemarituzumab were reduced visual acuity, punctuate keratitis, anaemia, neutropenia, nausea, corneal epithelial defect, and dry eye.

“The safety profile of bemarituzumab was primarily driven by corneal adverse events, including transient decreases in visual acuity,” Rha said. “Importantly, these ocular effects were mostly reversible with appropriate management, underscoring the drug’s manageable tolerability in the context of targeted FGFR inhibition.”

“Results from FORTITUDE-101, together with ongoing evaluation in the FORTITUDE-102 trial, will further define the benefit–risk profile of bemarituzumab in FGFR2b-overexpressing G/GEJC, potentially shaping future first-line standards of care for this biomarker-selected subgroup,” according to Rha and colleagues. [https://oncodaily.com/oncolibrary/fortitude-101-bema-gastric-cancer]