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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT04949256.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Shane Walton, PhD, and Lauren D’Angelo, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The authors thank Ravipati Sarath (of Merck & Co., Inc., Rahway, NJ, USA) for their assistance with this analysis.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

C. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Knight, Pfizer; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. F. Rivera: Financial Interests, Personal and Institutional, Advisory Board: MSD, Lilly, Astellas, BMS, Roche, Amgen, Merck, Servier; Financial Interests, Personal and Institutional, Invited Speaker: MSD, Lilly, Astellas, BMS, Roche, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, BMS, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Funding: MSD, AstraZeneca, BMS, Roche, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca, Amgen, Servier. S. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD, Bristol Myers Squibb, Ono. L. Yu, S. Shah, P. Bhagia: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. L. Shen: Financial Interests, Personal, Other, Consulting fees: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, BI, Sanofi, Roche, Servier, AZ; Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Alphamab Oncology, Yaojie Ankang (Nanjing) Technology Co., Ltd., BeiGene, Ltd., Qiyu Biotechnology (Shanghai) Co., Ltd., BriSTAR Immunotech; Financial Interests, Institutional, Local PI: Merck Healthcare KGaA, Roche; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceuticals, Innovent, BeiGene, Ltd., Qilu Pharmaceutical, NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.