Overview
Bemarituzumab (anti-FGFR2b) is an Fc-optimized monoclonal antibody that is designed to block fibroblast growth factors (FGFs) from binding and activating FGFR2b, inhibiting several downstream pro-tumor signaling pathways and potentially slowing cancer progression. The FIGHT trial evaluated bemarituzumab plus chemotherapy (mFOLFOX6) versus placebo plus chemotherapy alone in patients with FGFR2b positive, HER2 negative first-line unresectable locally advanced or metastatic gastric or GEJ cancer. In the study, treatment with bemarituzumab plus chemotherapy demonstrated clinically significant and substantial improvements in the primary endpoint of progression-free survival (PFS) and secondary endpoint of overall survival (OS) in the patient population with FGFR2b overexpression which accounts for 38% of HER2 negative patients. Based on this, the FDA granted bemarituzumab Breakthrough Therapy Designation. Zai Lab has an exclusive license for bemarituzumab in greater China, and we collaborated with Five Prime (subsequently acquired by Amgen) on the Phase 2 FIGHT trial in greater China. Two global phase 3 clinical studies for FGFR2b overexpression in first-line patients with unresectable locally advanced or metastatic gastric or GEJ cancer are ongoing (with China’s participation).
Mechanism of Action
Bemarituzumab has a dual mechanism of action: 1) it binds to the extracellular domain of FGFR2b, inhibiting the binding of FGF to the FGFR2b and thereby blocking FGFR2b signal transduction and inhibits tumor growth; 2) The afucosylated structure of Bemarituzumab enhances its affinity for natural killer (NK) cells, inducing enhanced antibody-dependent cellular cytotoxicity (ADCC). This facilitates NK cell recruitment to achieve potential tumor cell lysis.