65O - Phase 3 LEAP-008 study of lenvatinib plus pembrolizumab versus docetaxel for metastatic non-small cell lung cancer (NSCLC) that progressed on a PD-(L)1 inhibitor and platinum-containing chemotherapy

Background

Lenvatinib plus pembrolizumab (len + pembro) has shown efficacy in patients (pts) with advanced melanoma and renal cell carcinoma that progressed on a PD-(L)1 inhibitor. LEAP-008 was an open-label, phase 3 study of len + pembro vs docetaxel (doce) for metastatic NSCLC that progressed on a PD-(L)1 inhibitor and platinum-containing chemotherapy (NCT03976375).

Methods

Pts with stage IV squamous or nonsquamous NSCLC, any PD-L1 status, progression after prior anti–PD-(L)1 therapy and platinum-containing chemo (sequential or concomitant), and no indication for EGFR-, ALK-, or ROS1-targeted therapy were randomized 4:4:1 to len 20 mg/d QD PO plus ≤35 cycles of pembro 200 mg Q3W IV, doce 75 mg/m² Q3W IV, or len 24 mg/d QD PO. Dual primary endpoints were OS and PFS for len + pembro vs doce. Secondary endpoints included ORR for len + pembro vs doce, ORR for len + pembro vs len, and safety. PFS and ORR were assessed per RECIST 1.1 by blinded, independent central review. Superiority of len + pembro vs doce was assessed at interim analysis 1 (IA1) for ORR, at interim analysis 2 (IA2) for PFS, and at final analysis (FA) for OS. ORR for len + pembro vs len was assessed at IA2. All P values are one-sided.

Results

422 pts were randomized to len + pembro (n=185), doce (n=189), or len (n=48). Median study follow-up at FA was 31.8 mo (range, 16.5-48.7). Len + pembro did not significantly improve OS, PFS, or ORR vs doce (Table). Treatment-related AE rates for len + pembro vs doce vs len at FA were 59.7% vs 48.6% vs 57.4% for grade ≥3 and 3.9% vs 1.1% vs 6.4% for grade 5. Table: 65O

Conclusions

Len + pembro did not improve efficacy vs doce in stage IV NSCLC that progressed after prior anti–PD-(L)1 therapy and platinum-containing chemotherapy. The len + pembro safety profile was as expected based on prior studies. More effective therapies for this population of high unmet need are required.

Clinical trial identification

NCT03976375; first posted June 6, 2019.

Editorial acknowledgement

Medical writing assistance was provided by Melanie A. Leiby, PhD, an employee of 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

N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda, Janssen. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Novartis, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President: ASEICA (Spanish Association of Cancer Research); Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Incyte, Merck Serono; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, Novartis, Roche/Genentech, Pfizer. R. Hui: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Eisai, Merck, Oncosec, Amgen, Takeda, Zai Lab; Financial Interests, Personal, Invited Speaker: MSD, Novartis, AstraZeneca, Eli Lilly, Janssen; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Eli Lilly, Janssen, MSD, Novartis, Oncosec, Roche, Seagen, Corvus; Financial Interests, Personal, Steering Committee Member: MSD, AstraZeneca; Non-Financial Interests, Personal, Member: ASCO, IASLC, Medical Oncology Group of Australia (MOGA); Non-Financial Interests, Personal, Other, Member of IASLC Education Committee: IASLC. S. Baka: Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Boehringer, Eli-Lilly, Merck, Novartis, Takeda, Sanofi-Aventis, Glaxo, Daiichi Sankyo, Amgen, Regeneron, Roche; Financial Interests, Personal, Advisory Role: BMS, Servier, Merck. F. Bigot: Financial Interests, Personal and Institutional, Invited Speaker: MSD, AstraZeneca; Financial Interests, Institutional, Speaker’s Bureau: Takeda, Sanofi, MSD, AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: MSD, AstraZeneca, RevMed. M. Nishio: Financial Interests, Personal, Invited Speaker, lectures fee: Ono Pharmaceuticals; Financial Interests, Personal, Invited Speaker, lectures: Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen; Financial Interests, Personal, Invited Speaker, lectures,: Lilly. A. Smolin: Financial Interests, Personal, Invited Speaker: Novartis, Roche, R-Farm; Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad; Financial Interests, Personal and Institutional, Local PI: MSD, BMS, AstraZeneca, Biocad, Lilly, Roche. S. Ahmed: Financial Interests, Personal and Institutional, Coordinating PI: MSD. A. Schoenfeld: Financial Interests, Personal, Other, Consulting: Johnson and Johnson, KSQ Therapeutics, Perceptive Advisors, Legend Biotech, Iovance Biotherapeutics, Oppenheimer and Co; Financial Interests, Personal, Advisory Board: BMS, Enara Bio, Umoja Biopharma, Prelude Therapeutics, Immunocore, Amgen, Lyell Immunopharma, Heat Biologics; Financial Interests, Personal and Institutional, Steering Committee Member: Merck; Financial Interests, Institutional, Steering Committee Member: Iovance Biotherapeutics; Financial Interests, Institutional, Local PI: GSK, Achilles Therapeutics, BMS; Financial Interests, Personal, Local PI: Synthekine; Financial Interests, Institutional, Coordinating PI: Obsidian; Non-Financial Interests, Personal, Principal Investigator: GSK, Achilles Therapeutics, Iovance Therapeutics, BMS, Merck, PACT pharma. D.L. Cortinovis: Financial Interests, Personal, Advisory Board, fee for consulting activity: MSD, BMS, Roche, Sanofi Genzyme, Amgen, AstraZeneca, Novartis. V.P. Di Noia: Financial Interests, Personal and Institutional, Expert Testimony: Takeda, Roche, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Principal Investigator: Dizal. H. Linardou: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Merck, Takeda, Bristol Myers Squibb, Lilly, Pfizer, GSK; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Amgen, Novartis; Financial Interests, Personal, Stocks/Shares: BioPath Innovations S.A.; Financial Interests, Personal and Institutional, Local PI: Bristol Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist; Financial Interests, Institutional, Local PI: GSK; Non-Financial Interests, Personal, Principal Investigator: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Leadership Role, Elected Chair of the Scientific Committee: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Member of Board of Directors: Women 4 Oncology - Hellas, Fairlife Lung Cancer Care, Hellenic Cooperative Oncology Group, Hellenic Foundation for Cancer Research; Non-Financial Interests, Personal, Leadership Role, Legal Representattive: Women 4 Oncology- Hellas. J. Gainor: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Genentech/Roche, Takeda, Lilly, Moderna, AstraZeneca, Pfizer, Novartis, iTeos, Karyopharm, Silverback Therapeutics, GlydeBio, BeiGene, AI Protein, Mirati; Financial Interests, Personal, Stocks/Shares, Immediate family member is an employee. Note: Ironwood Pharmaceuticals is not involved in any oncology drug development. It is focused on gastroenterology.: Ironwood Pharmaceuticals; Financial Interests, Personal and Institutional, Coordinating PI: Novartis; Financial Interests, Institutional, Coordinating PI: Genentech, Bristol Myers Squibb, Merck, AstraZeneca, Moderna, Jounce, Alexo; Financial Interests, Institutional, Local PI: Palleon, Scholar Rock. C.E. Okpara: Financial Interests, Personal, Full or part-time Employment: Eisai Ltd. X. Deng: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. D.A. Kush: Financial Interests, Personal, Full or part-time Employment, Former employee: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. A. Song: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS Bio; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, Kanaph Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS Bio; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: Daan Biotherapeutics. All other authors have declared no conflicts of interest.