Amgen’s FORTITUDE-101 evaluating bemarituzumab in combination with mFOLFOX6 in 1L gastric/gastroesophageal junction cancer shows no meaningful improvement in OS at final analysis, resulting in a setback for Amgen’s bema program.

On October 20^th, 2025, Amgen presented overall survival (OS) from the final analysis of its P3 FORTITUDE-101 (NCT05052801) trial, which evaluated bemarituzumab (bema, anti-FGFR2b) in combination with mFOLFOX6 in patients with 1L HER2-negative FGFR2b-positive gastric/gastroesophageal junction cancer (GC/GEJC). This data was presented as a late-breaking abstract presentation (#LBA10) at ESMO 2025. 

Assessment

• Despite showing statistically significant and clinically meaningful survival benefit at the planned interim analysis, at final analysis, bema + mFOLFOX6 showed no meaningful improvement in OS over mFOLFOX6 (14.5 vs 13.2 mo, HR: 0.82) in 1L HER2-negative FGFR2b-positive GC/GEJC
  • FORTITUDE-101 no longer poses a competitive threat to STAR-221 as this data is not considered practice changing and does not have a regulatory path forward
• Gr 3+ TRAEs occurred in 60% of patients dosed with bema vs 18% in the control arm. Most common Gr ≥3 TEAEs were corneal AEs resulting in visual acuity reduction (33% vs 0%)

• FORTITUDE-101’s lackluster result represents a setback for Amgen’s bema program. However, topline data from P1b/3 FORTITUDE-102 evaluating bema + nivolumab (PD-1) + chemo (a direct competitor to STAR-221 in the FGFR2b+ population) is anticipated EOY 2025 or H1 2026 and will elucidate the therapeutic potential of a biomarker directed therapy in combination with a PD-1 agent and chemo in 1L G/GEJ
  • If data are positive, earliest possible US approval for FORTITUDE-102 would be Q1 2027 with an EU approval in Q2 2027
  • FGFR2b protein overexpression (FGFR2b >10% IHC 2+/3+) is observed in only 16% of patients with GEC

Phase 3 FORTITUDE-101 results presented at ESMO 2025:

• Study Information 
  • Phase 3 FORTITUDE-101 (NCT05052801): bemarituzumab + mFOLFOX6 vs placebo + mFOLFOX6 in 1L HER2-negative FGFR2b-overexpressed GC/GEJ 
    • FGFR2b overexpression was defined as 2+/3+ staining in ≥10% of tumor cells by centrally performed IHC testing
  • N= 547 (bema + FOLFOX6 vs placebo + FOLFOX6)
    • FGFR2b ≥10% subset (bema vs placebo): 159 vs 165
    • Safety analysis: 275 vs 267
    • Of note, 43% of the patients were randomized in the last 6 months of the enrollment period which lasted from May 2022 – June 2024
  • 1EP: OS
  • 2EP: PFS, ORR, DOR, DCR, QoL, safety, plasma concentration of bemarituzumab + mFOLFOX6, anti-bemarituzumab antibody formation

Summary of FORTITUDE-101 data:

• At planned interim analysis, OS benefit favored bemarituzumab across the prespecified subgroups of CPS ≥5 (HR: 0.42) and Gastric adenocarcinoma (HR: 0.48)