FIGHT: A randomized, double-blind, placebo-controlled, phase II study of bemarituzumab (bema) combined with modified FOLFOX6 in 1L FGFR2b+ advanced gastric/gastroesophageal junction adenocarcinoma (GC).

4010 Background: Bema is a first-in-class humanized IgG1 monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b). Results from the FIGHT study showed an improvement in progression-free survival (PFS), overall survival (OS), and overall response rate with the addition of bema to mFOLFOX6 in FGFR2b+, non HER2+ GC. This report provides updated analyses of patient (pt) subgroups, additional data on ocular adverse events (AEs), and the median OS result for the bema+mFOLFOX6 combination. Methods: Pts were treated with mFOLFOX6 and randomized 1:1 to bema (15 mg/kg) or placebo (pbo) every 2 weeks (wks) with an additional 7.5 mg/kg bema/pbo dose on cycle 1 day 8. Eligible pts had unresectable locally advanced or metastatic GC not known to be HER2+, and had FGFR2b overexpression (any 2+/3+ staining) by centrally performed immunohistochemistry (IHC+) or FGFR2 amplification by circulating tumor DNA (ctDNA+). Results: Of the 155 pts who were randomized, 149 (96%) were FGFR2b+ by IHC, 26 (17%) by ctDNA, and 20 (13%) by both. 96 pts (62%) had tumors with FGFR2b IHC 2+/3+ in ≥10% of tumor cells. The proportion of pts with ctDNA+ or with ≥5% or ≥10% tumor cells FGFR2b+ by IHC was similar across geographic regions. Bema showed a benefit vs pbo across pre-specified subgroups including age, gender, geographic region, and prior adjuvant therapy. Patients with FGFR2b overexpression irrespective of ctDNA gene amplification benefited from bema: IHC+/ctDNA- PFS hazard ratio (HR) 0.63 (95% CI 0.4, 0.99), OS HR 0.66 (95% CI 0.39, 1.12); IHC+/ctDNA+ PFS HR 0.15 (95% CI 0.02, 1.18), OS HR 0.10 (95% CI 0.01, 0.83). Frequency and severity of ocular AEs were similar for the overall enrolled population and for pts with ≥5% or ≥10% FGFR2b+ by IHC. Corneal AEs in the bema arm increased in frequency and severity over time; 10.5% (0% G3) wk 1-8 vs 44.1% (15.3% G3) wk ≥25. Following discontinuation of study treatment, subsequent anti-cancer therapy was balanced in the 2 arms (bema 53%; pbo 49%). With a median follow-up of 12.5 months (mo), the bema arm had a median OS of 19.2 mo (95%CI: 13.6, not reached) vs 13.5 mo (95%CI: 9.3, 15.9) for placebo (HR:0.60 95%CI: 0.38, 0.94) for the intent-to-treat population; for the subset of pts with ≥10% FGFR2b+ by IHC, the median OS for bema was 25.4 mo (95%CI: 13.8, not reached) vs 11.1 mo (95% CI: 8.4, 13.8) for placebo (HR: 0.41 95%CI: 0.23, 0.74). Conclusions: The addition of bema to mFOLFOX6 improved the OS of 1L FGFR2b+ GC pts vs mFOLFOX6 alone. Outcomes favored bema across pre-specified subgroups. Pts with overexpression of FGFR2b even without ctDNA amplification demonstrated a benefit from the addition of bema to mFOLFOX6, supporting further evaluation of bema in tumors with FGFR2b overexpression without the requirement for gene amplification. Clinical trial information: NCT03694522.