Phase I results from the phase 1/3 FIGHT study evaluating bemarituzumab and mFOLFOX6 in advanced gastric/GEJ cancer (GC).

Abstract

91 Background: GC with FGFR2b overexpression or FGFR2 amplification is associated with a poor prognosis. Bemarituzumab (bema, FPA144) is a first-in-class humanized monoclonal IgG1 antibody that selectively blocks FGFR2b and triggers antibody-dependent cell-mediated cytotoxicity. With favorable safety and activity as a single agent in 2L+ patients with FGFR2b+ GC, the global, randomized, double-blind, placebo-controlled FIGHT study (NCT03343301) is evaluating the front-line combination of bema with mFOLFOX6. We report here the results from the phase I evaluation of the combination. Methods: Patients (pts) with unresectable, locally advanced or metastatic gastrointestinal malignancy (irrespective of FGFR2b status) for whom mFOLFOX6 would be appropriate were eligible for enrollment in the phase I. Her2+ disease or prior treatment with FGF-FGFR inhibitors was not allowed. All pts in the Phase 1 received mFOLFOX6 combined with bema in Q2W cycles. Cohort 1 (3+3) began with bema 6 mg/kg and cohort 2 (Rolling-6) bema 15 mg/kg with one dose of 7.5 mg/kg on C1D8. A dose-limiting toxicity (DLT) evaluation window of 28 days was used for both cohorts. Results: Cohorts 1 and 2 treated 3 pts and 9 pts respectively with a median of 4 and 2 prior lines of therapy. As of the iDMC data-cut on July 24, 2018, the median duration of treatment was 15 wks for cohort 1 and 4 wks for cohort 2; 6/9 pts in cohort 2 continue on treatment. No DLTs were identified. No adverse events (AEs) led to treatment discontinuation. There were no newly identified bema-related toxicities and the only ≥ Gr 2 AE attributable to bema in cohort 2 was fatigue (1 pt/Gr 2). The most common AEs overall were fatigue (6 pts/50%), nausea, vomiting and diarrhea (5 pts/42% each) and were generally attributed to FOLFOX or underlying disease. The ≥ Gr 3 AEs present in ≥ 1 pt were fatigue and neutropenia (2 pts/Gr 3 each). mFOLFOX6 did not affect bema exposure and all evaluable pts in cohort 2 achieved the target ≥ 60 µg/mL trough concentration by day 15. 2/7 pts at the data-cut had FGFR2b+ GC. Conclusions: Bema in combination with mFOLFOX6 has acceptable safety to proceed with the cohort 2 dose to the phase III portion of the FIGHT trial in previously untreated patients with FGFR2b+ GC. Clinical trial information: NCT03343301.