Data from the phase 2 FIGHT study indicated that the monoclonal antibody bemarituzumab may be a promising treatment when combined with mFOLFOX6 for patients with advanced gastric or gastro-esophageal junction adenocarcinoma.
Although it did not achieve a statistically significant progression-free survival (PFS) improvement, bemarituzumab resulted in promising clinical benefit in combination with modified 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (Eloxatin; mFOLFOX6) in the treatment of patients with HER2 non-positive FGFR2b-selected gastric or gastro-esophageal junction adenocarcinoma, according to findings from the phase 2 FIGHT study (NCT03694522) published in the Lancet Oncology.
After a median follow-up of 10.9 months (IQR 6.3-14.2), median PFS was found to be 9.5 months (95% CI, 7.3-12.9) in the bemarituzumab group vs 7.4 months (95% CI, 5.8-8.4) in the placebo group (HR 0.68; 95% CI, 0.44-1.04; P = .073). Median overall survival (OS) was not reached (NR; 95% CI 13.8-NR) in the bemarituzumab group and was 12.9 months (95% CI, 9.1-15.0) in the placebo group (HR 0.58; 95% CI, 0.35-0.95; P = .027). Moreover, data from a post-hoc analysis that included a long-term follow-up and a median time on study of 12.5 months (interquartile range [IQR], 6.6-18.5) resulted in a median OS of 19.2 months (95% CI, 13.6-NR) in the bemarituzumab group and 13.5 months (95% CI, 9.3-15.9) in the placebo group (HR 0.60; 95% CI, 0.38-0.94).
“Bemarituzumab is the first drug to specifically target FGFR2b protein overexpression in cancer, and although treatment with bemarituzumab did not significantly improve [PFS] over placebo in the total population, treatment might improve outcomes for patients with HER2-negative, FGFR2b-overexpressing gastric adenocarcinoma tumors,” the investigators wrote.
This randomized, double-blind, placebo-controlled study evaluated 155 patients with either an overexpression of tumor FGFR2b (96%), amplification of tumor FGFR2 (17%), or both (13%). The median patient age was 60 years (IQR 51-67), the majority of whom were men (72%). Most patients were either Asian (57%) or White (39%). Most patients in the bemarituzumab and placebo arms, respectively, had gastric adenocarcinoma as their primary disease site (86% vs 91%).
Participants were treated with either bemarituzumab (n = 77) or matched placebo (n = 78) intravenously at a dose of 15 mg/kg every 2 weeks, with a single additional dose of 7.5 mg/kg on day 8 of the first cycle. Both arms also received intravenous mFOLFOX6 every two weeks at the following dosages: oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², and 5-FU as a 400 mg/m² bolus followed by 2400 mg/m² over roughly 46 hours. The median duration of treatment was 24 weeks (IQR, 16.1-33.8) and 26 weeks (IQR 16.0-37.7) in the bemarituzumab and placebo groups, respectively. Bemarituzumab treatment was halted in the event of any grade 3 non-corneal adverse effects (AEs) and was resumed at either the original or a reduced dose (6 mg/kg) if the toxicity resolved within 28 days. Dose reduction was mandated for a second grade 3 AE, and discontinuation was mandated for a third grade 3/4 AE. Treatment with mFOLFOX6 continued regardless of these reductions or discontinuations.
In terms of secondary findings, the objective response rate was 47% (95% CI, 35%-59%) vs 33% (95% CI, 23%-45%) in the bemarituzumab and placebo groups, respectively. Additionally, median duration of response was 12.2 months (95% CI, 5.5-15.6) for patients in the bemarituzumab cohort compared with 7.1 months (95% CI, 4.3-11.7) for those in the placebo cohort.
Notably, these results were consistent with those observed in a prespecified exploratory analysis of patients with FGFR2b overexpression.
AEs occurred in all patients save for 1 in the placebo group. The most common of grade 3 or higher AEs in thebemarituzumab vs placebo cohorts, respectively, were decreased neutrophil counts (30% vs 35%), cornea disorders (24% vs 0%), neutropenia (13% vs 9%), stomatitis (9% vs 1%), and anemia (8% vs 13%). Fifty-four percent of patients who received bemarituzumab discontinued treatment vs 36% of those who received placebo. A total of 3 treatment-related deaths occurred in the bemarituzumab group, whereas none occurred in the placebo group.
The combination will be further assessed in a population of patients with previously untreated advanced gastric or gastro-esophageal junction adenocarcinoma, including in the phase 3 FORTITUDE-101 (NCT05052801) and FORTITUDE-102 (NCT05111626) trials.
Wainberg ZA, Enzinger PC, Kang YK, 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. Published online October 13, 2022. doi:10.1016/S1470-2045(22)00603-9