Bemarituzumab in First-Line Gastric Cancer — FORTITUDE Trials

Bemarituzumab is a first-in-class monoclonal antibody that targets FGFR2b (fibroblast growth factor receptor 2b), a key driver in a subset of gastric cancers characterized by FGFR2b overexpression. The FORTITUDE clinical trial program explores the efficacy and safety of bemarituzumab in various settings, primarily focusing on its use in first-line treatment for gastric cancer. Below is a detailed breakdown of the FORTITUDE trials relevant to first-line gastric cancer:

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### **1. FORTITUDE-101:**

• **Objective:** Evaluated the combination of bemarituzumab with chemotherapy (mFOLFOX6) versus chemotherapy plus placebo in patients with FGFR2b-positive gastric cancer.
• **Results:**
• Bemarituzumab plus chemotherapy significantly **improved overall survival (OS)** compared to chemotherapy alone.
• **Median OS:**
• Bemarituzumab + mFOLFOX6: **17.9 months**
• Placebo + mFOLFOX6: **12.5 months**
• **Hazard Ratio (HR):** 0.61 (indicating a 39% reduction in the risk of death).
• **Statistical Significance:** p = 0.005.
• This trial demonstrates the potential benefit of bemarituzumab in improving survival for patients with FGFR2b-positive gastric cancer.

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### **2. FORTITUDE-102:**

• **Objective:** A Phase 1b/3 study designed to evaluate bemarituzumab in combination with chemotherapy and nivolumab versus chemotherapy and nivolumab alone in FGFR2b-positive first-line gastric cancer.
• **Status:** This trial was **stopped**. The specific reasons for discontinuation are not provided in the context, but it is common for trials to be stopped due to various factors, including safety concerns, lack of efficacy, or strategic decisions.

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### **3. FORTITUDE-103:**

• **Objective:** A Phase 1b/2 study investigating bemarituzumab in combination with or without nivolumab across different oral chemotherapy regimens for first-line gastric cancer patients.
• **Update:** The trial has successfully **completed patient enrollment**, indicating that the study is progressing as planned. Results from this study will provide further insights into the potential of bemarituzumab in combination with different therapeutic approaches.

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### **Broader Development – FORTITUDE-30:**

• While not limited to gastric cancer, the Phase 1b/2 **FORTITUDE-30 basket study** is exploring bemarituzumab as a monotherapy in patients with solid tumors that overexpress FGFR2b. This study could expand the use of bemarituzumab beyond gastric cancer to other FGFR2b-driven malignancies.

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### **Conclusion:**

The FORTITUDE clinical trial program underscores the promise of bemarituzumab as a targeted therapy for FGFR2b-positive gastric cancer, particularly in the first-line setting. The positive results from FORTITUDE-101 highlight its potential to improve overall survival when combined with chemotherapy. The ongoing FORTITUDE-103 study and the broader FORTITUDE-30 basket trial may further solidify bemarituzumab's role in treating FGFR2b-overexpressing tumors, while the discontinuation of FORTITUDE-102 highlights the challenges of combining multiple therapies. Future results from these studies will be crucial to defining bemarituzumab's place in the treatment landscape for gastric cancer and potentially other cancers.