First-Line Bemarituzumab Plus Chemo Hits OS End Point in FGFR2b+ Advanced Gastric Cancer

The addition of bemarituzumab to mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs placebo plus chemotherapy in patients with HER2-negative, unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer harboring FGFR2b overexpression, meeting the primary end point of the phase 3 FORTITUDE-101 trial (NCT05052801).¹

Findings announced by Amgen also showed that the most common treatment-emergent adverse effects (AEs) reported in more than 25% of patients treated in the bemarituzumab arm comprised reduced visual acuity, punctate keratitis, anemia, neutropenia, nausea, corneal epithelium defect, and dry eye. Although instances of ocular AEs were consistent with prior phase 2 data and occurred in both treatment arms, they were reported at a higher rate frequency and severity in the phase 3 bemarituzumab group.

Detailed data from the prespecified interim analysis will be presented at an upcoming medical meeting.

“Most patients with gastric cancer are diagnosed at an advanced stage, with poor prognosis, low survival rates, and limited therapeutic options,” Jay Bradner, MD, executive vice president of Research and Development at Amgen, stated in a news release. “These first positive topline 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.”

FORTITUDE-101 Overview

The randomized, multicenter, double-blind, placebo-controlled trial enrolled patients at least 18 years of age with histologically documented locally advanced unresectable or metastatic gastric or GEJ cancer not amenable to curative therapy.² Patients needed to be positive for FGFR2b overexpression, defined 2+ or 3+ staining on at least 10% of tumor cells per centrally performed immunohistochemistry (IHC).

Other key inclusion criteria included an ECOG performance status of 0 or 1; evaluable disease that could be measurable or non-measurable per RECIST 1.1 criteria; no contraindications to mFOLFOX6; and adequate organ and bone marrow function.

Patients were excluded if they received prior treatment in the metastatic or unresectable setting; however, previous neoadjuvant, adjuvant, and perioperative therapy was permitted if completed more than 6 months prior to first dose of study treatment. Other exclusion criteria included any prior treatment with a selective FGFR inhibitor; HER2-positive disease; untreated or symptomatic central nervous system disease or brain metastases; and clinically significant cardiac disease.

A total of 547 patients enrolled across the study at 300 sites across 37 countries.¹ Patients were randomly assigned to receive bemarituzumab plus mFOLFOX6 or placebo plus mFOLFOX6.

Along with the primary end point of OS, secondary end points included progression-free survival, objective response rate, duration of response, disease control rate, quality of life, and safety.²

Bemarituzumab is also being investigated in the phase 3 FORTITUDE-102 study (NCT05111626), where patients with previously untreated gastric cancer are being randomly assigned to receive bemarituzumab in combination with chemotherapy and nivolumab (Opdivo) or placebo plus chemotherapy and nivolumab. Data from this study are expected to read out in the second half of 2025.¹

After the safety and tolerability of the combination of bemarituzumab, chemotherapy, and nivolumab were evaluated in the first nonrandomized part of the study, patients with locally advanced unresectable or metastatic, histologically documented gastric or GEJ adenocarcinoma are being randomly assigned between the 2 arms in the second part of the study. Notably, patients being enrolled to the randomized portion are required to have centrally confirmed FGFR2b overexpression per IHC.

References

1. Amgen announces positive topline phase 3 results for bemarituzumab in fibroblast growth factor receptor 2b (FGFR2b) positive first-line gastric cancer. News release. Amgen. June 30, 2025. Accessed June 30, 2025. https://www.amgen.com/newsroom/press-releases/2025/06/amgen-announces-positive-topline-phase-3-results-for-bemarituzumab-in-fibroblast-growth-factor-receptor-2b-fgfr2b-positive-firstline-gastric-cancer
2. Bemarituzumab or placebo plus chemotherapy in gastric cancers with fibroblast growth factor receptor 2b (FGFR2b) overexpression (FORTITUDE-101). ClinicalTrials.gov. Updated February 7, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05052801
3. Bemarituzumab plus chemotherapy and nivolumab versus chemotherapy and nivolumab for FGFR2b overexpressed untreated advanced gastric and gastroesophageal junction cancer. (FORTITUDE-102). ClinicalTrials.gov. Updated June 12, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05111626