Amgen announced that its Phase 3 FORTITUDE-101 clinical trial evaluating bemarituzumab plus chemotherapy met its primary endpoint of overall survival at a pre-specified interim analysis. The study demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to placebo plus chemotherapy in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer with FGFR2b overexpression who are non-HER2 positive.
Addressing Critical Unmet Medical Need
Gastric cancer represents the fifth leading cause of cancer-related death worldwide, with nearly one million new cases and over 650,000 deaths globally each year. Most patients with gastric cancer are diagnosed at an advanced stage, with poor prognosis, low survival rates and limited therapeutic options.
"These first positive top-line results of an FGFR2b targeted monoclonal antibody from our Phase 3 FORTITUDE-101 study mark a meaningful advance in the development of effective targeted therapy for gastric cancer," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen.
Trial Design and Patient Population
FORTITUDE-101 was a randomized, multi-center, double-blind, placebo-controlled Phase 3 study comparing bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6 as first-line therapy. The trial spanned 300 sites across 37 countries, with 547 patients enrolled.
The primary outcome measure was overall survival in patients with FGFR2b ≥10% 2+/3+ tumor cell staining, with FGFR2b overexpression defined as 2+/3+ staining in ≥10% of tumor cells by centrally performed immunohistochemistry testing. Key secondary outcome measures included progression-free survival and overall response rate. Patients known to be human epidermal growth factor receptor 2 (HER2) positive were excluded from the trial.
Safety Profile and Adverse Events
The most common treatment-emergent adverse events (>25%) in patients treated with bemarituzumab plus chemotherapy were reduced visual acuity, punctate keratitis, anaemia, neutropenia, nausea, corneal epithelium defect and dry eye. While ocular events were consistent with the Phase 2 experience and observed in both arms, they occurred with greater frequency and severity in the Phase 3 bemarituzumab arm.
FORTITUDE-101 included more comprehensive ocular-related monitoring than previous studies of bemarituzumab to better characterize these events.
FGFR2b as Therapeutic Target
The FGFR2b protein is an emerging biomarker which, when overexpressed, promotes aberrant signaling leading to tumor cell proliferation. FGFR2b protein is overexpressed by gastric and gastroesophageal junction tumor cells in approximately 38% of patients with advanced disease. In approximately 16% of patients with advanced gastric and gastroesophageal junction cancer, FGFR2b protein overexpression is observed on ≥10% of tumor cells by immunohistochemistry.
Development Partnership and Future Studies
FORTITUDE-101 was conducted with the support of Zai Lab, which holds co-development and commercialization rights for bemarituzumab for mainland China, Hong Kong, Macau, and Taiwan.
A Phase 3 study of bemarituzumab plus chemotherapy and nivolumab is also ongoing in patients with first-line gastric cancer, with a data readout anticipated in the second half of 2025. Detailed results from the FORTITUDE-101 trial will be shared at a future medical meeting.
