Abstract 1223P
Background
LEAP-015 (NCT04662710) is a randomized, open-label, 2-part, phase III study of the safety and efficacy of len + pembro + chemo as a first-line treatment for advanced/metastatic gastroesophageal adenocarcinoma. We report findings from part 1, the safety run-in, of LEAP-015.
Methods
Eligible patients (pts) had untreated, HER2-negative, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma, measurable disease per RECIST v1.1, and ECOG performance status 0 or 1. In part 1, pts received induction with IV pembro 400 mg Q6W (×2) + oral len 8 mg QD + investigator choice of chemo (capecitabine + oxaliplatin [CAPOX] Q3W ×4 or 5-fluorouracil + leucovorin + oxaliplatin [mFOLFOX6] Q2W ×6) and consolidation with pembro 400 mg Q6W for ≤16 doses + len 20 mg QD; dose-limiting toxicities (DLTs), defined as selected prespecified grade ≥3 adverse events (AEs) or any-grade thromboembolic events, were evaluated for 21 days after the first dose of study intervention. If ≥3 DLTs occurred in either oxaliplatin-containing regimen, then enrollment in part 2 was delayed to allow for examination of safety data and to consider design changes. In part 1, the primary end point was safety and tolerability in all pts.
Results
In part 1, 15 pts received ≥1 dose of len + pembro + chemo. 1 DLT of grade 3 asthenia occurred in the CAPOX cohort and 1 DLT of grade 4 neutropenia occurred in the FOLFOX cohort. Median time from first dose to data cutoff (Oct 13, 2021) was 7 mo (range, 7-9). Treatment-related AEs occurred in 14 pts (93%), with grade 3/4 treatment-related AEs in 8 pts (53%). 4 pts discontinued any drug because of a treatment-related AE and no pt discontinued all drugs because of a treatment-related AE. No pt died because of a treatment-related AE. No grade ≥3 immune-mediated AEs or infusion reactions occurred.
Conclusions
In the safety run-in of LEAP-015, len + pembro + chemo was associated with a manageable safety profile in the first-line treatment of advanced/metastatic gastroesophageal adenocarcinoma. Part 2 is currently enrolling and will evaluate the efficacy and safety of len + pembro + chemo vs chemo in this same pt population.
Clinical trial identification
NCT04662710 Release date: December 10, 2020.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Lauren D’Angelo, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, Takeda, Pfizer, ONO PHARMACEUTICAL, MSD, TAIHO PHARMACEUTICAL, Novartis, AbbVie, GlaxoSmithKline, Daiichi Sankyo, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Company Limited, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Astellas, ONO PHARMACEUTICAL, Daiichi Sankyo, TAIHO PHARMACEUTICAL, CHUGAI PHARMACEUTICAL, MSD, Medi Science, Eisai, Amgen. C. Rojas: Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, AstraZeneca, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Merck, Bristol Myers Squibb, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb. L. Bai: Financial Interests, Personal, Invited Speaker: Eli Lilly, ONO, TTY; Non-Financial Interests, Personal, Principal Investigator: Eisai. F. Ghiringhelli: Financial Interests, Personal, Funding: Astra, Roche; Financial Interests, Personal, Invited Speaker: Roche, MSD; Financial Interests, Personal, Advisory Board: MSD. L. Wyrwicz: Financial Interests, Personal, Advisory Role: GlaxoSmithKline, BeiGene; Financial Interests, Personal, Research Grant: MSD, Bristol Myers Squibb, BeiGene, Roche, AstraZeneca. Y.Y. Janjigian: Financial Interests, Personal, Advisory Role: Pfizer, Merck, Bristol Myers Squibb, Merck Serono, Daiichi Sankyo, Rgenix, Bayer, Immugene, AstraZeneca, Eli Lilly, Zymeworks, Basilea Pharmaceutical, Michael J. Hennessy Associates, Paradigm, Seattle Genetics, Clinical Care Options, Axis Medical Education, Research to Practice; Financial Interests, Personal, Stocks/Shares: Rgenix, RGENIX; Financial Interests, Institutional, Research Grant: Bayer, Rgenix, Bristol Myers Squibb, Merck, Eli Lilly, NCI, Department of Defense, Cycle for Survival, Fred's Team, Genentech/Roche, Bayer, Bristol Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, NCI, RGENIX; Financial Interests, Personal, Invited Speaker: Amerisource Bergen, Arcus Biosciences AstraZeneca, Axis Medical Education, Basilea Pharmaceutica, Bayer, Bristol Myers Squibb, Clinical Care Options, Daiichi-Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline Imedex, Imugene, Lynx Health, Merck, Merc. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Hutchinson Medipharma, HalioDX SAS, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. E. Van Cutsem: Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Inghelheim, Bristol Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KgaA, Novartis, Roche, Servier; Financial Interests, Personal and Institutional, Advisory Board: AbbVie, Array, Astellas, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Eli Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks. A. Wang: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. M.G. Miller: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Leadership Role: Merck. C. Shih: 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. P.E. Yanez Weber: Financial Interests, Personal, Advisory Role: MSD Oncology, Bristol Myers Squibb/Medarex, AstraZeneca Chile; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, straZeneca Chile; Financial Interests, Institutional, Other, Honoraria: MSD Chile, Bristol Myers Squibb, AstraZeneca Chile, Sanofi/Regeneron. All other authors have declared no conflicts of interest.