Background
Phase II, double-blind, placebo-controlled RCT in 155 patients with previously untreated, unresectable, locally advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma with FGFR2b overexpression (IHC 2+/3+) or FGFR2 gene amplification (ctDNA). Bemarituzumab is a humanized anti-FGFR2b monoclonal antibody.
Interventions and follow up
Arm A: mFOLFOX6 + bemarituzumab 15 mg/kg Q2W with an additional 7.5 mg/kg dose on cycle 1 day 8 (n=77)
Arm B: mFOLFOX6 + placebo (n=78)
Primary endpoint: Investigator-assessed PFS
Secondary endpoints: OS, ORR, safety
Median follow up: minimum 24 mo at final analysis
Arm B: mFOLFOX6 + placebo (n=78)
Primary endpoint: Investigator-assessed PFS
Secondary endpoints: OS, ORR, safety
Median follow up: minimum 24 mo at final analysis
Results
mPFS: 9.5 mo vs 7.4 mo, HR 0.68, 95% CI 0.44-1.04, P=.07 (Arm A vs B)
mOS: Not reached vs 12.9 mo, HR 0.58, 95% CI 0.35-0.95, P=.03 (final: 19.2 mo vs 13.5 mo)
ORR: 53% vs 40%
Median DOR: 12.2 mo vs 7.1 mo
FGFR2b ≥10% subgroup: PFS HR 0.43 (95% CI 0.26-0.73); OS HR 0.52 (95% CI 0.31-0.85)
mOS: Not reached vs 12.9 mo, HR 0.58, 95% CI 0.35-0.95, P=.03 (final: 19.2 mo vs 13.5 mo)
ORR: 53% vs 40%
Median DOR: 12.2 mo vs 7.1 mo
FGFR2b ≥10% subgroup: PFS HR 0.43 (95% CI 0.26-0.73); OS HR 0.52 (95% CI 0.31-0.85)
Adverse events
Overall: Grade ≥3 AEs 83% vs 74%; serious AEs 32% vs 36% (Arm A vs B)
Ocular: Corneal events (dry eye, keratitis, punctate keratitis) 67% vs 10%, grade ≥3 24% vs 0%; corneal toxicities resolved in 60% (median time to resolution 27 wks)
GI/mucosal: Stomatitis 31.6% vs 13.0%
Ocular: Corneal events (dry eye, keratitis, punctate keratitis) 67% vs 10%, grade ≥3 24% vs 0%; corneal toxicities resolved in 60% (median time to resolution 27 wks)
GI/mucosal: Stomatitis 31.6% vs 13.0%
Conclusions
Adding bemarituzumab to mFOLFOX6 in first-line FGFR2b-positive gastric/GEJ cancer improved OS and showed a strong PFS trend, with benefit enriched in tumors with high FGFR2b expression. Corneal toxicity is a distinctive class effect requiring monitoring.
Key Limitations
Phase II, modest sample size; primary PFS endpoint did not reach statistical significance. Significant corneal and mucosal toxicity. Requires FGFR2b biomarker selection. Confirmatory phase III trials (FORTITUDE-101/-102) ongoing.
Clinical Context
Bemarituzumab is investigational and not FDA/EMA approved as of 2026. FIGHT established FGFR2b as a targetable biomarker in gastric cancer and prompted the phase III FORTITUDE program. ESMO recognizes FGFR2b as an emerging biomarker; testing is not yet routine standard of care.
References
Wainberg Z et al, JCO, 2021, PMID 31094225
Final analysis: Wainberg ZA et al, Lancet Oncol, 2022, PMID: 36328000
Final analysis: Wainberg ZA et al, Lancet Oncol, 2022, PMID: 36328000