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).
Daniel V.T. Catenacci, Yoon‐Koo Kang, Anwaar Saeed, Kensei Yamaguchi, Shukui Qin, Keun‐Wook Lee, In-Ho Kim, Sang Cheul Oh, Jin Li, Hacı Mehmet Türk, Alexandra Teixeira, Christophe Borg, Erika Hitre, Anghel Adrian Udrea, Giovanni Gerardo Cardellino, R. Guardeño, Siddhartha Mitra, Yingsi Yang, Peter C. Enzinger, Zev A. Wainberg
Abstract
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.