FIGHT: A phase 3 randomized, double-blind, placebo controlled study evaluating (bemarituzumab) FPA144 and modified FOLFOX6 (mFOLFOX6) in patients with previously untreated advanced gastric and gastroesophageal cancer with a dose finding phase 1 lead-in.

TPS4135 Background: FGFR2b overexpression and FGFR2 gene amplification occurs in approximately 10% of patients with gastric cancer (GC) and is associated with a poor prognosis and the presence of metastases. Bemarituzumab, a first-in-class afucosylated, humanized IgG1 monoclonal antibody, selectively binds to FGFR2b, inhibiting ligand binding and blocking receptor activation and downstream signaling. Bemarituzumab is glycoengineered to enhance antibody-dependent cell-mediated cytotoxicity (ADCC). A phase 1 study of bemarituzumab monotherapy in solid tumors (Catenacci D, Rha S, Bang YJ, et.al. ASCO 2017) identified no dose-limiting toxicities. The reported response rate was 19% (4/21) with median duration of response of 15.4 weeks in patients with late-line GC and high FGFR2b overexpression. Based on the safety and activity profile of bemarituzumab monotherapy in GC, we designed a phase 3 trial with safety run-in of bemarituzumab in combination with mFOLFOX6. Methods: The FIGHT study (FPA144-004; NCT03343301) is a global, randomized, double-blind, placebo-controlled phase 3 trial evaluating bemarituzumab and mFOLFOX6 in first-line patients with advanced GC. Patients with unresectable locally advanced, or metastatic GC are eligible if tumors have FGFR2 amplification by circulating tumor DNA (ctDNA) or FGFR2b overexpression by immunohistochemistry (IHC). Eligible patients are randomized 1:1 to bemarituzumab + mFOLFOX6 versus placebo + mFOLFOX6. Bemarituzumab or placebo dosing will continue every 2 weeks until radiographic or clinical disease progression, or intolerable toxicity. The primary endpoint is overall survival (OS) and key secondary endpoints include investigator-assessed progression-free survival (PFS) and objective response rate (ORR). The primary analyses will be event-based. The FIGHT Phase 3 trial is preceded by a Phase 1 safety evaluation in gastro-intestinal tumors without selection for FGFR2b. This portion of the trial initiated in December 2017 and is currently in progress with accrual to phase 3 expected in mid-2018. Clinical trial information: NCT03343301.