1223P First-line lenvatinib (Len) + pembrolizumab (Pembro) + chemotherapy (Chemo) vs chemo in advanced/metastatic gastroesophageal adenocarcinoma: LEAP-015 safety run-in

LEAP-015 (NCT04662710) is a randomized, open-label, 2-part, phase III study of the safety and efficacy of len + pembro + chemo as a first-line treatment for advanced/metastatic gastroesophageal adenocarcinoma. We report findings from part 1, the safety run-in, of LEAP-015. Eligible patients (pts) had untreated, HER2-negative, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma, measurable disease per RECIST v1.1, and ECOG performance status 0 or 1. In part 1, pts received induction with IV pembro 400 mg Q6W (×2) + oral len 8 mg QD + investigator choice of chemo (capecitabine + oxaliplatin [CAPOX] Q3W ×4 or 5-fluorouracil + leucovorin + oxaliplatin [mFOLFOX6] Q2W ×6) and consolidation with pembro 400 mg Q6W for ≤16 doses + len 20 mg QD; dose-limiting toxicities (DLTs), defined as selected prespecified grade ≥3 adverse events (AEs) or any-grade thromboembolic events, were evaluated for 21 days after the first dose of study intervention. If ≥3 DLTs occurred in either oxaliplatin-containing regimen, then enrollment in part 2 was delayed to allow for examination of safety data and to consider design changes. In part 1, the primary end point was safety and tolerability in all pts. In part 1, 15 pts received ≥1 dose of len + pembro + chemo. 1 DLT of grade 3 asthenia occurred in the CAPOX cohort and 1 DLT of grade 4 neutropenia occurred in the FOLFOX cohort. Median time from first dose to data cutoff (Oct 13, 2021) was 7 mo (range, 7-9). Treatment-related AEs occurred in 14 pts (93%), with grade 3/4 treatment-related AEs in 8 pts (53%). 4 pts discontinued any drug because of a treatment-related AE and no pt discontinued all drugs because of a treatment-related AE. No pt died because of a treatment-related AE. No grade ≥3 immune-mediated AEs or infusion reactions occurred. In the safety run-in of LEAP-015, len + pembro + chemo was associated with a manageable safety profile in the first-line treatment of advanced/metastatic gastroesophageal adenocarcinoma. Part 2 is currently enrolling and will evaluate the efficacy and safety of len + pembro + chemo vs chemo in this same pt population.