1534P First-line lenvatinib (len) plus pembrolizumab (pembro) and chemotherapy (chemo) for metastatic esophageal squamous cell carcinoma (mESCC): Safety run-in results from the phase III LEAP-014 study

LEAP-014 (NCT04949256) is a randomized, two-part, open-label, phase III study evaluating the safety and efficacy of len + pembro + chemo vs pembro + chemo in patients (pts) with previously untreated mESCC. Results from part 1 (safety run-in cohort) are reported. Eligible pts had confirmed previously untreated mESCC; measurable disease per RECIST v1.1 by investigator; and ECOG PS score ≤1. In part 1, pts received induction with IV pembro 400 mg Q6W×2 cycles + oral len 8 mg QD + chemo (cisplatin + 5-FU [FP] Q3W×4 cycles or paclitaxel + cisplatin [TP] Q3W×4 cycles) and consolidation with IV pembro 400 mg Q6W for ≤16 doses + oral len 20 mg QD. Pts were treated until disease progression or unacceptable toxicity. Primary end points for part 1 were dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs. DLTs were evaluated for 21 days after the first dose; if ≥3 DLTs occurred in the TP or FP cohort, then part 2 could be delayed to further examine safety data and consider study design changes. At data cut-off (February 2, 2023), 13 pts were treated (FP: 7; TP: 6). Median time from first dose to data cut-off was 16.6 mo (range, 15.9-17.3) and 5.6 mo (4.6-6.2) with len + pembro + FP and len + pembro + TP, respectively. Median (range) age was 64 y (43-77) and 66 y (53-71), respectively. One DLT of grade 3 acute kidney injury associated with increased creatinine level and 1 DLT of grade 3 hypokalemia occurred in the FP cohort; no DLTs were reported in the TP cohort. No pt discontinued because of a DLT. No treatment-related deaths occurred. ORR and DOR will be reported. Part 1 (safety run-in) of LEAP-014 showed that len + pembro + chemo had acceptable safety and tolerability in pts with previously untreated mESCC, allowing initiation of part 2. Part 2 is ongoing and will evaluate the efficacy and safety of len + pembro + chemo vs pembro + chemo as first-line therapy for mESCC.