189P - Safety run-in results from LEAP-014: First-line lenvatinib (len) plus pembrolizumab (pembro) and chemotherapy (chemo) for metastatic esophageal squamous cell carcinoma (ESCC)

Background

The randomized, 2-part, open-label, phase 3 LEAP-014 study (NCT04949256) is being conducted to evaluate the safety and efficacy of len + pembro + chemo vs pembro + chemo in patients with previously untreated metastatic ESCC. Results from the safety run-in cohort (part 1) are reported.

Methods

Eligible patients had histologically or cytologically confirmed previously untreated metastatic ESCC, measurable disease per RECIST v1.1 by investigator assessment, and ECOG PS score 0 or 1. In part 1, patients received induction with pembro 400 mg IV Q6W ×2 cycles + len 8 mg PO QD + chemo (cisplatin + 5-FU [FP cohort] Q3W ×4 cycles or paclitaxel + cisplatin [TP cohort] Q3W ×4 cycles) and consolidation with pembro 400 mg IV Q6W for ≤16 cycles + len 20 mg PO QD. Treatment continued 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 cutoff (February 2, 2023), 13 patients were treated (FP cohort, n = 7; TP cohort, n = 6). Median time from first dose to data cutoff was 16.6 months (range, 15.9-17.3) and 5.6 months (4.6-6.2) with len + pembro + FP and len + pembro + TP, respectively. Median (range) age was 64 years (43-77) and 66 years (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 patient discontinued because of a DLT and no treatment-related deaths occurred. Preliminary efficacy results will be reported.

Conclusions

Part 1 (safety run-in) of LEAP-014 showed that len + pembro + chemo had acceptable safety and tolerability in patients with previously untreated metastatic ESCC, allowing initiation of part 2. Part 2 is ongoing and is evaluating the efficacy and safety of len + pembro + chemo vs pembro + chemo as first-line therapy for patients with metastatic ESCC.

Clinical trial identification

NCT0494926.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Obinna Ezeokoli, PhD, and Andrea Humphries, PhD, CMPP, 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.

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

S. Yamamoto: Financial Interests, Personal, Invited Speaker: Ono, Bristol Myers Squibb, MSD. C. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, 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 Herrero: Financial Interests, Personal and Institutional, Advisory Board: MSD, Lklly, Astellas, BMS, Roche, Amgen, Merck-Serono, Servier; Financial Interests, Personal and Institutional, Invited Speaker: MSD, Lklly, Astellas, BMS, Roche, Amgen, Merck-Serono, Servier, Novartis; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, BMS, Amgen, Merck-Serono, Servier, Novartis; Financial Interests, Personal and Institutional, Funding: MSD, AstraZeneca, BMS, Roche, Amgen, Merck-Serono, Servier, Novartis; Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca, Amgen, Servier. L. Yu: Financial Interests, Institutional, Full or part-time Employment: Merck & Co.; Financial Interests, Institutional, Stocks/Shares: Merck & Co. S. Shah: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. 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 Pharmaceutical, Innovent, BeiGene, Ltd., NovaRock Biotherapeutics Limited, Qilu Pharmaceutical. All other authors have declared no conflicts of interest.