Bemarituzumab for treatment of previously untreated advanced and/or metastatic gastric and gastroesophageal cancer (GC): Final analysis of a randomized phase 2 trial (FIGHT)

Bemarituzumab is a first-in-class, humanized IgG1 monoclonal antibody, selective for fibroblast growth factor receptor 2b (FGFR2b). In FIGHT, bemarituzumab + mFOLFOX6 demonstrated clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with placebo + mFOLFOX6 among patients with FGFR2b-overexpressing GC (primary analysis data cutoff: September 23, 2020); here, we report the FIGHT final analysis (24 months after the last patient was enrolled).

Patients with GC, assessed for FGFR2b overexpression by immunohistochemistry (IHC) analysis (any 2+/3+ staining) and/or FGFR2 gene amplification by circulating tumor DNA, were randomized 1:1 to receive bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. Eligible patients were not known to be HER2 positive. The primary endpoint of PFS was centrally assessed.

In the bemarituzumab (N=77) and placebo (N=78) groups, 59.7% and 66.7% of patients, respectively, had FGFR2b overexpression in ≥10% of tumor cells by IHC staining. One patient in each group was not treated. The data cutoff was May 13, 2022. Median PFS was 9.5 months (95% confidence interval [CI], 7.3-13.7) in the bemarituzumab group and 7.4 months (95% CI, 5.7-8.4) in the placebo group (hazard ratio [HR], 0.72 [95% CI, 0.49-1.08]). Median OS was 19.2 months (95% CI, 13.6-24.2) in the bemarituzumab group and 13.5 months (95% CI, 9.3-15.9) in the placebo group (HR, 0.77 [95% CI, 0.52-1.14]). Objective response rate (ORR) was 48.1% and 33.3% in the bemarituzumab and placebo groups, respectively; the difference in ORR was 14.4% (95% CI, -1.5 to 30.3). Treatment benefit was more pronounced in patients with FGFR2b overexpression in ≥10% of tumor cells by IHC staining: PFS: HR, 0.43 (95% CI, 0.26-0.73); OS: HR, 0.52 (95% CI, 0.31-0.85); and difference in ORR: 20.0% (95% CI, 0.6%-39.4%). No new safety concerns were identified. In the bemarituzumab and placebo groups, 100% and 98.7% of patients, respectively, had at least one treatment-emergent adverse event (TEAE); 82.9% and 75.3% of patients, respectively, reported grade ≥3 TEAEs. Study drug discontinuation due to TEAEs was higher in the bemarituzumab group (40.8%) than in the placebo group (5.2%). Study drug was discontinued for any-grade corneal events not resolved within 28 days; therefore, 77.4% (24/31) of patients discontinued bemarituzumab. In the bemarituzumab and placebo groups, corneal TEAEs were reported in 67.1% and 10.4% of patients, respectively, and were resolved/downgraded to grade 1 in 46.1% and 9.1% of patients, respectively. Median time to onset and resolution of ocular events was 16.9 weeks and 24.4 weeks, respectively, for the bemarituzumab group and 11.6 weeks and 1.4 weeks, respectively, for the placebo group.

After 24 months of follow-up, patients with FGFR2b overexpression treated with bemarituzumab + mFOLFOX6 continued to show clinically meaningful outcomes over patients treated with placebo + mFOLFOX6; more pronounced efficacy was observed in patients with ≥10% of tumor cells with 2+/3+ FGFR2b IHC staining intensity. Randomized phase 3 trials focused on patients with ≥10% of tumor cells to confirm the observed clinical benefit of bemarituzumab are ongoing.

NCT03694522.

Medical writing support was provided by Julie Gegner, PhD, of Amgen Inc., and Utkarsha A Singh, PhD, of Cactus Communications, funded by Amgen Inc.

Amgen Inc.

This study was funded by Five Prime Therapeutics, Inc.

Z. Wainberg: Advisory / Consultancy: Daiichi, Ipsen, BMS, Bayer, Amgen, Astra Zeneca, Arcus, Seagen, Pfizer, Astellas, Novartis, Merck; Research grant / Funding (self): Arcus, BMS; Research grant / Funding (institution): Plexxikon, Merck; Travel / Accommodation / Expenses: Amgen. K. Lee: Honoraria (self): Sanofi-Aventis; Research grant / Funding (institution): Five Prime Therapeutics, Amgen. K. Yamaguchi: Honoraria (Institution): Taiho pharm; Speaker Bureau / Expert testimony: Daiichi Sankyo, Eli Lilly Japan, Ono pharm, Bristol Mayers Squibb, Merck biopharm. A. Saeed: Advisory / Consultancy: AstraZeneca, Bristol Myers Squibb, Exelixis, Pfizer, and Daiichi Sankyo; Research grant / Funding (institution): AstraZeneca, Bristol Myers Squibb, Merck, Clovis, Exelixis, Actuate therapeutics, Incyte Corporation, Daiichi Sankyo, Five prime therapeutics, Amgen, Innovent biologics, Dragonfly therapeutics, KAHR medical, and Biontech, . A. Zahlten-Kümeli: Shareholder / Stockholder / Stock options: Amgen; Full / Part-time employment: Amgen. K. Taylor: Shareholder / Stockholder / Stock options: Amgen Ltd; Full / Part-time employment: Amgen Ltd. P. Enzinger: Advisory / Consultancy: Arcus Biosciences, Astellas Pharma, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb/Celgene, Celgene, Coherus Biosciences, Daiichi Sankyo, Five Prime Therapeutics, IDEAYA Biosciences, ISTARI Oncology, Legend Biotech, Lilly, loxo, Merck, Novartis, Ono Pharmaceutical, SERVIER, Taiho Pharmaceutical, Takeda, Turning Point Therapeutics, Xencor, Zymeworks. All other authors have declared no conflicts of interest.