1526P Phase Ib Results of Bemarituzumab (bema)+mfolfox6+nivolumab (NIVO) for Advanced Gastric/gastroesophageal Junction Cancer (G/GEJC): Fortitude-102 Part 1

In the phase (ph) 2 FIGHT trial, BEMA+mFOLFOX6 had promising efficacy in patients with FGFR2b-selected G/GEJC. FORTITUDE-102 comprises part 1 (open-label ph1b) evaluated the safety and tolerability of BEMA+mFOLFOX6+NIVO and part 2 (randomized ph3) the safety and efficacy compared with placebo. Here, we present the results of part 1. Up to 20 patients (pts) with/without FGFR2b overexpression could be enrolled. The initial dose of BEMA was 15 mg/kg IV Q2W with one 7.5 mg/kg dose on cycle 1 day 8. The dose-limiting toxicity (DLT) period was 28 days. At least 6 pts were treated at a dose level with less than 33% incidence of DLTs to determine the recommended ph3 dose (RP3D). An ad hoc review was performed 6mo after the DLT period. Eight pts (50-71 y) were enrolled and evaluated for DLTs: 6 pts were men, 4 pts were Asian, and 4 pts were White. No DLTs were reported; no new safety signals were identified. Mean exposures for the first 3 cycles and estimated terminal elimination half-life (7-11 days) were consistent with historical data. No meaningful BEMA exposure changes were observed with the addition of NIVO, indicating no drug interactions. The RP3D was 15 mg/kg Q2W with one 7.5mg/kg dose on cycle 1 day 8. Six mo post-DLT period, the median treatment duration was ∼34 weeks (8-40). Four pts had 6 serious AEs (n=1 AE [hyponatremia] considered BEMA-related); 7 pts had 13 grade ≥3 AEs (n=4 [neutropenia, mucositis, hyponatremia, and delirium] in 2pts considered BEMA-related). Five pts reported 8 ocular AEs of grades ≤2, with a median time to onset of ∼17 weeks. No AEs led to BEMA discontinuation. Treatment was interrupted in 4 pts due to BEMA-related AEs (1 was ocular related). PR was seen in 3 pts, SD in 4 pts, and PD in 1 pt. BEMA was stopped for consent withdrawal in 1pt and PD in 2pts. Updated data will be presented at the congress. This is the first time a combination of BEMA, mFOLFOX6, and NIVO is assessed. In part 1, consistent safety and PK profiles suggest no negative interaction, with no new safety signals after 6 mo.