Bemarituzumab Prolongs Survival in FGFR2b-Overexpressing Gastric/GEJ Cancers

Zev A. Wainberg, MD

Treatment with bemarituzumab plus combination chemotherapy in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in the FIGHT study (NCT03694522) achieved promising clinical efficacy.

The agent showed improvement in the primary end point of progression-free survival (PFS) vs placebo, but the result was not statistically significant.1

“This is the first antibody to target FGFR2B in clinical development. Based on most of the literature in gastric cancer, this could represent a target in up to 30% of metastatic gastric cancer. This drug could work in the 5%-7% of patients with FGFR amplified gastric cancer and a large group who expresses FGFR2B on the protein level,” said Zev A. Wainberg, MD, a medical oncologists/hematologist, professor of Medicine at UCLA, and co-director of the UCLA GI Oncology Program, in a statement to Targeted Oncology^TM.

Bemarituzumab, an FGFR2b monoclonal antibody, was previously granted breakthrough therapy designation in combination with the chemotherapy combination of modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for the treatment of patients with FGFR2b-overexpressing, HER2-negative, advanced gastric or GEJ adenocarcinoma based on preliminary results from the randomized, double-blind, placebo-controlled FIGHT study.

Primary analysis results were from 155 adult patients randomly assigned to receive either bemarituzumab at 15 mg/kg of bodyweight with mFOLFOX6 consisting of oxaliplatin 85 mg/m², leucovorin 400 mg/m², and 5-fluorouracil as a 400 mg/m² bolus followed by 2400 mg/m² over 46 hours (n = 77) or matching placebo with mFOLFOX6 (n = 78). All patients were 18 years of age or older with an ECOG performance status of 0-1. All patients in the study continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death.

At a median follow-up of 10.9 months (interquartile range, 6.3-14.2 months), the median PFS was 9.5 months (95% CI, 7.3-12.9 months) in the bemarituzumab arm compared with 7.4 months (95% CI, 5.8-8.4 months) in the placebo arm (HR, 0.68; 95% CI, 0.44-1.04; P = .073). The median overall survival was 19.2 months (95% CI, 13.6-not reached) in the experimental arm vs 13.5 months (95% CI, 9.3-15.9 months) in the placebo arm (HR, 0.60; 95% CI, 0.38-0.94).

The objective response rate observed with bemarituzumab in the study was 47% (95% CI, 35%-59%) vs 33% (95% CI, 23%-45%) in the placebo arm, for a difference of 13% (95% CI, –3-29; P = .11). The median duration of response was 12.2 months (95% CI, 5.5-15.6 months) in the bemarituzumab arm vs 7.1 months (95% CI, 4.3-11.7 months) in the placebo group.

Safety results from the FIGHT study showed that 30% of patients in the bemarituzumab group experienced grade 3 or higher decreased neutrophil count. The most common adverse events (AEs) in the bemarituzumab group vs the placebo arm were cornea disorder (24% vs none), neutropenia (13% vs 9%), stomatitis (9% vs 1%), and anemia (8% vs 13%). Serious AEs occurred in 32% of the bemarituzumab arm compared with 36% of the placebo arm.

Treatment-related AEs were seen in 12% of the bemarituzumab arm vs 19% of the placebo arm. Corneal events of any grade occurred in 67% of patients who received bemarituzumab vs 10% of the in the placebo arm. Corneal events were high grade in 24% of the bemarituzumab group.

There were 3 treatment-related deaths in the study, and all of them occurred in the bemarituzumab arm. Events leading to death were sepsis and pneumonia.

“In the FIGHT study, we demonstrated that the group of patients with metastatic HER2-negative FGFR2-selected gastric cancer had greater PFS and OS if they received FOLFOX plus bemarituzumab over FOLFOX plus placebo. This represents a new target of interest in gastric cancer and randomized phase 3 trials are ongoing to confirm this benefit,” Wainberg said.

_REFERENCES:

_{Wainberg ZA, Enzinger PC, Kang Y, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2020;23(11): 1430-1440. doi:10.1016/S1470-2045(22)00603-9}