Image Credit: Adobe Stock Images/mi_viri
Key Takeaways
- Bemarituzumab Shows Survival Benefit: The Phase III FORTITUDE-101 trial met its primary endpoint, with bemarituzumab plus chemotherapy significantly improving overall survival in FGFR2b-positive, HER2-negative gastric and gastric or gastroesophageal junction (G/GEJ) cancer.
- Ocular Adverse Events (AEs) Noted: While generally consistent with earlier findings, ocular AEs—including visual changes and dry eye—were more frequent and severe in the bemarituzumab treatment arm.
- Gastric Cancer Remains Global Concern: Despite declining incidence in the United States, gastric cancer remains the fifth most common cancer worldwide, with East Asia accounting for a significant share of global cases.
Results from the Phase III FORTITUDE-101 trial showed Amgen’s bemarituzumab combined with chemotherapy (mFOLFOX6) significantly improved overall survival (OS) in patients with previously untreated unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer who are FGFR2b-positive and HER2-negative. According to the company, the therapy met its primary endpoint at a pre-specified interim analysis, demonstrating both statistical significance and clinical relevance.1
“Most patients with gastric cancer are diagnosed at an advanced stage, with poor prognosis, low survival rates and limited therapeutic options,” said Jay Bradner, MD, EVP, research and development, Amgen, in a press release.
FORTITUDE-101 Trial Design and Endpoints
- The randomized, multi-center, double-blind, placebo-controlled FORTITUDE-101 trial (NCT05052801) evaluated the efficacy of bemarituzumab plus chemotherapy compared to placebo plus chemotherapy in 547 patients.
- Patients were randomly assigned to receive either an intravenous (IV) infusion of bemarituzumab plus mFOLFOX6, administered as a combination of oxaliplatin and leucovorin as IV infusions, or an IV placebo in combination with mFOLFOX6 administered the same way.
- The primary endpoint of the trial was OS in patients with FGFR2b ≥10% 2+/3+ tumor cell staining, while key secondary endpoints included progression-free survival and overall response rate.1,2
- Amgen stated that detailed efficacy and safety results from the trial will be presented at an upcoming medical meeting.
Safety Profile
- Common treatment-related adverse events associated with bemarituzumab plus chemotherapy included visual acuity changes, punctate keratitis, anemia, neutropenia, nausea, corneal epithelium defects, and dry eye.
- Although ocular events were observed in both treatment arms and were consistent with findings from the Phase II trial, they were more frequent and more severe in patients receiving bemarituzumab in the Phase III study.1
Epidemiology and Global Context
According to the American Cancer Society, it is estimated that there will be approximately 30,300 new cases of stomach cancer and 10,780 deaths by the end of 2025. It accounts for around 1.5% of all cancers diagnosed in the United States annually. Stomach cancer is most common in people over 65 years of age, who make up 60% of all cases. The median age at diagnosis is 68. It is more common in men, who have a one in 101 chance of developing stomach cancer, while women have a one in 155 chance.
Over the past 10 years, new cases have declined by 1.5% each year in the United States. However, it remains more prevalent in other parts of the world, especially in East Asia. Greater reliance on refrigeration for food storage has reduced consumption of salted and smoked foods, which are known risk factors for stomach cancer. Additionally, fewer people are now infected with Helicobacter pylori (H. pylori), a bacterium believed to play a major role in the disease’s development.3
Global Burden of Disease
According to the World Cancer Research Fund, stomach cancer is the fifth most common cancer globally. It is also the fourth most common cancer in men and the seventh most common in women. In 2022, China led the world in new cases with 358,672—significantly more than in the United States.4
“These first positive top-line results of an FGFR2b targeted monoclonal antibody from our Phase III FORTITUDE-101 study mark a meaningful advance in the development of effective targeted therapy for gastric cancer,” said Bradner, in the press release.
References
AMGEN ANNOUNCES POSITIVE TOPLINE PHASE 3 RESULTS FOR BEMARITUZUMAB IN FIBROBLAST GROWTH FACTOR RECEPTOR 2b (FGFR2b) POSITIVE FIRST-LINE GASTRIC CANCER. Amgen. June 30, 2025. Accessed July 2, 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
Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (FORTITUDE-101). Clinicaltrials.gov. Accessed July 2, 2025. https://clinicaltrials.gov/study/NCT05052801
Key Statistics About Stomach Cancer. American Cancer Society. Accessed July 2, 2025. https://www.cancer.org/cancer/types/stomach-cancer/about/key-statistics.html
Stomach cancer statistics. World Cancer Research Fund. Accessed July 2, 2025. https://www.wcrf.org/preventing-cancer/cancer-statistics/stomach-cancer-statistics/#stomach-cancer-deaths