Leap-005: Evaluating The Safety And Efficacy Of Lenvatinib And Pembrolizumab In Patients Previously Treated For Ovarian Cancer, A Multi-Cohort Phase 2 Study

Introduction/Background Lenvatinib, an antiangiogenic multiple receptor tyrosine kinase inhibitor, plus pembrolizumab, a programmed death-1 immune checkpoint inhibitor, demonstrated promising clinical benefit in a previous phase Ib/II trial across several cancer types (ClinicalTrials.gov, NCT02501096). We assessed clinical outcomes with lenvatinib plus pembrolizumab in patients with ovarian cancer in the ongoing, open-label, multicohort, phase II LEAP-005 study (ClinicalTrials.gov, NCT03797326). Methodology Female patients aged ≥18 years with histologically/cytologically confirmed metastatic/unresectable ovarian cancer, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), Eastern Cooperative Oncology Group (ECOG) performance status 0/1, and 3 prior lines of therapy were enrolled. Patients received lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks for 35 cycles, or until confirmed disease progression or unacceptable toxicity. Primary endpoints were objective response rate (ORR; response assessed every 9 weeks for 54 weeks, then every 12 weeks, by blinded independent central review per RECIST v1.1) and safety. Secondary endpoints included disease control rate, duration of response, and progression-free survival. Results 31 patients with ovarian cancer received ≥1 dose of lenvatinib plus pembrolizumab in LEAP-005 (median age 62 years [range 40–76]); median study follow-up was 7.8 months (range, 4.6–12.4) as of April 10, 2020. ORR was 32% (95% confidence interval, 17–51); other efficacy endpoints were also favorable (table 1). Treatment-related adverse events occurred in 29 (94%) patients (table 1). Conclusion Lenvatinib plus pembrolizumab demonstrated encouraging efficacy and manageable safety in patients with heavily pretreated ovarian cancer, including those with prior platinum failure and those with previous bevacizumab exposure. Disclosures Antonio Gonzalez-Martin: Advisory/Consultancy: Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Mersana, Merck Sharp & Dohme, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio; Speaker Bureau: AstraZeneca, PharmaMar, Roche, GSK; Research Grant/Funding: Roche, TESARO: A GSK Company; Travel/Accommodation/Expenses: AstraZeneca, PharmaMar, Roche, TESARO: A GSK Company Hyun Cheol Chung: Grants/Research Support: Lilly, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, Beigene, Incyte; Honoraria: Merck-Serono, Lilly/Foundation Medicine; Consultation: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, Beigene, Amgen, Zymework Esma Saada-Bouzid: Advisory/Consultancy: BMS, MSD; Travel/Accommodation: AstraZeneca, BMS, MSD Eduardo Yanez: Consultant/Advisory Board: BMS, Merck Serono; Research Grant: Amgen, Pfizer, Astellas, BMS, Roche, Abbvie, MSD Helene Senellart: Nothing to disclose. Philippe A. Cassier: Honoraria: Novartis, Roche/Genentech, Blueprint Medicines, Amgen, AstraZeneca; Research Funding: Novartis, Roche/Genentech, Lilly, Blueprint Medicines, Bayer, AstraZeneca, Celgene, Plexxikon, Abbvie, BMS, Merck Serono, MSD, Taiho Pharmaceutical, Toray Industries, Transgene, Loxo, GSK, Innate Pharma, Janssen (all paid to institution); Travel, Accomodations, Expenses: Roche, Amgen, Novartis, BMS, MSD, Netris Pharma. Bristi Basu: Consultancy: GenMab (paid to institution); Advisory Board: Roche, Eisai Europe Limited, research grant from Celgene Ltd (all paid to institution); Speakers Bureau: Eisai Europe Ltd (paid to institution); Travel and Registration for Congress: Bayer. Razi Ghori: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Peter Kubiak: employee of Eisai Inc., Woodcliff Lake, NJ, USA Alan Smith: employee of Eisai Ltd., Hatfield, UK Kevin Norwood: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Zarnie Lwin: Received honoraria for consulting, advisory role or travel sponsorship from AbbVie; AstraZeneca; BMS; Roche; and Merck