New Combination Therapies Using the Antibody Bemarituzumab for Advanced FGFR2b-Positive Gastric Cancer

Stomach cancer is one of the more common types of cancer of the digestive system and usually arises from glandular cells in the stomach lining. The development of stomach cancer is a complex process influenced by the interaction of various risk factors. One of the most important causes is a chronic infection with the bacterium Helicobacter pylori, which can damage the stomach lining over many years and lead to persistent inflammation. Other risk factors include smoking, excessive alcohol consumption, and certain pre-existing conditions such as stomach ulcers. In some cases, there is also a family or genetic predisposition. Stomach cancer typically develops gradually over many years from initially benign changes in the lining. FGFR2b is a protein on the surface of tumor cells that plays an important role in cell growth and division. It is a receptor located on the cell surface that transmits growth signals into the cell. Overexpression of FGFR2b—that is, an increased number of the protein on cancer cells—thus leads to faster tumor growth. Treatment for FGFR2b-positive gastric cancer depends on the stage of the disease and typically involves a combination of surgery, chemotherapy, and/or targeted therapies. For advanced gastric cancer, chemotherapy and/or targeted therapy with an FGFR2b inhibitor such as bemarituzumab may be considered, especially if overexpression of the receptor has been detected. Bemarituzumab is a monoclonal antibody currently in clinical development for the treatment of gastric and gastroesophageal junction carcinoma. The drug is therefore not yet approved for treatment. Bemarituzumab specifically targets the FGFR2b receptor and blocks the binding of growth factors to this receptor, which can inhibit tumor growth. The BEMARA study combines bemarituzumab with various standard chemotherapy regimens to specifically investigate the benefits of this combination. Standard chemotherapy regimens such as irinotecan, paclitaxel with ramucirumab, or trifluridine/tipiracil generally inhibit the growth of cancer cells, regardless of their molecular characteristics. By combining both approaches, researchers hope to increase efficacy, overcome resistance, and control tumor growth more effectively than with chemotherapy alone.

The goal of this Phase 2a study is to evaluate three different combinations of bemarituzumab with one approved standard chemotherapy regimen each. To this end, bemarituzumab will be combined with irinotecan (Group 1), paclitaxel plus ramucirumab (Group 2), or trifluridine/tipiracil (Group 3). Assignment to a treatment group will be determined by the treating medical staff. Before treatment begins, a tissue sample from the tumor will be tested for the presence of the target protein FGFR2b. During treatment, efficacy (e.g., reduction in tumor mass), disease progression, survival, and possible side effects will be monitored regularly. Patients’ quality of life is also systematically assessed. The follow-up period is approximately 33 months. The goal is to determine which combination is most effective and well-tolerated in order to further develop targeted therapy for FGFR2b-positive gastric cancer. The primary endpoint of the study is the objective response rate (ORR), which is the proportion of patients in whom a measurable reduction in tumor size is observed during treatment.

Eligible participants are adults aged 18 and older with advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (GEJ) who have already received at least one prior line of therapy (at least two for Group 3) and are not candidates for potentially curative surgical removal of the tumor. Additionally, a positive FGFR2b result in the tumor tissue is a prerequisite for participation. Patients with HER2-positive tumors may participate provided they have previously received appropriate therapy. Excluded are, among others, patients with untreated brain metastases, certain eye diseases, severe heart problems, or active infections.