Bemarituzumab for FGFR2b-Positive Gastric Cancer

In clinical trials involving patients with esophagogastric adenocarcinoma, treatments with monoclonal antibodies targeting transmembrane growth-factor receptors have largely failed. However, some trials did not use biomarkers to select patients most likely to respond to such therapy.

Investigators now report results of an industry-sponsored, international, randomized, double-blind, placebo-controlled, phase 2 trial (FIGHT) that used overexpression of fibroblast growth-factor receptor 2b (FGFR2b) or FGFR2 gene amplification to select advanced gastric cancer patients who might respond to bemarituzumab, a humanized monoclonal antibody blocking the FGFR2b receptor.

Of 910 screened participants with HER2-negative metastatic gastric or gastroesophageal junction cancer, 262 had FGFR2b overexpression (as determined by immunohistochemistry), 38 had FGFR2 gene amplification (as determined blood-based genomic profiling), and 26 had both FGFR2b overexpression and FGFR2 gene amplification. From this FGFR2b-positive group, 155 eligible patients (median age, 60; 72% male; 88% with gastric primaries; 17% with prior adjuvant therapy) were randomized to first-line treatment with mFOLFOX6 plus either bemarituzumab or placebo.

At a median follow-up of 10.9 months, the primary endpoint of progression-free survival trended superior with bemarituzumab compared with placebo (9.5 and 7.4 months; hazard ratio, 0.68; P=0.073), as did overall survival (19.2 and 13.5 months) and response rate (47% and 33%). The rate of serious adverse events was similar with either treatment. Bemarituzumab was associated with more stomatitis (9% vs. 1%) and more corneal toxicity (24% vs. 0%).