Bemarituzumab Demonstrates Promising Clinical Efficacy in FGFR2b-Selected Gastric or GEJ Adenocarcinoma

According to results from an exploratory phase 2 study, treatment with bemarituzumab showed promising clinical efficacy for patients with FGFR2b-selected gastric or gastroesophageal junction adenocarcinomas, despite there being no statistically significant improvement of progression-free survival (PFS) compared to placebo. Bemarituzumab is a “first-in-class, afucosylated, humanized, IgG1 anti-fibroblast growth factor receptor 2 isoform IIb (FGFR2b) monoclonal antibody,” wrote Zev Wainberg, MD, University of California Los Angeles Medical Center, Los Angeles, California, and colleagues.

In the double-blinded, FIGHT trial, 155 patients with HER2 non-positive, FGFR2b-selected gastric or gastroesophageal junction adenocarcinoma were enrolled across 17 countries between November 14, 2017, and May 8, 2020. Patients were randomized on a 1:1 basis to receive mFOLFOX6 (modified 5-fluorouracil, leucovorin, and oxaliplatin) intravenous every 2 weeks, and either 15 mg/kg bemarituzumab (n = 77) or a matched placebo (n = 78) intravenously every 2 weeks. The primary end point was PFS in the intention-to-treat population, with secondary end points including safety of all patients who received at least 1 dose of the assigned treatment.

At a median follow-up duration of 10.9 months, the median PFS of patients in the bemarituzumab group was 9.5 months (95% confidence interval [CI], 7.3 to 12.9), compared to 7.4 months (95% CI, 5.8 to 8.4) in the placebo group (hazard ratio [HR], 0.68; 95% CI, 0.44 to 1.04; P = .073).

The most common grade ≥3 adverse events were decreased neutrophil count (30% in the bemarituzumab group vs 35% in the placebo group), cornea disorder (24% vs none), neutropenia (13% vs 9%), stomatitis (9% vs 1%), and anemia (8% vs 10%). In the bemarituzumab group, 32% of patients reported serious treatment-emergent adverse events, compared to 36% in the placebo group. Serious mFOLFOX6 treatment-related adverse events were reported in 12% of patients in the bemarituzumab group and 19% in the placebo group.

All-grade corneal events, which was an adverse event of special interest, occurred in 67% of patients in the bemarituzumab group compared to 10% in the placebo group, with 18 (24%) patients in the bemarituzumab group reporting a grade 3 corneal event. There were 3 treatment-related deaths in the bemarituzumab group (2 due to sepsis, 1 due to pneumonia) and none in the placebo group.

Dr Wainberg and colleagues concluded, “despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy.” They added, “Confirmatory phase 3 trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreatment, FGFR2b-overexpressing, advanced gastric or gastroesophageal junction adenocarcinoma.”

Source:

Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomized, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. Published online October 13, 2022. doi:10.1016/S1470-2045(22)00603-9