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Poster Display session 1

4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)


28 Sep 2019


Poster Display session 1


Tumour Site

Non-Small Cell Lung Cancer


Martin Gutierrez


Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260


M. Gutierrez1, W. Lam2, M.D. Hellmann3, M.A. Gubens4, C. Aggarwal5, D.S.W. Tan6, E. Felip7, J.W.Y. Chiu8, J.S. Lee9, J.C. Yang10, E.B. Garon11, A. Basso12, H. Ma12, L. Fong13, A. Snyder12, J. Yuan12, R.S. Herbst14

Author affiliations

  • 1 Oncology, Hackensack University Medical Center, 07601 - Hackensack/US
  • 2 Medical Oncology, Fiona Stanley Hospital, Perth/AU
  • 3 Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 4 Oncology, UCSF Medical Center, San Francisco/US
  • 5 Medical Oncology, University of Pennsylvania, Philadelphia/US
  • 6 Oncology, SingHealth Duke NUS Academic Medical Centre, Singapore/SG
  • 7 Oncology, Vall d'Hebron University Hospital, Barcelona/ES
  • 8 Medicine, University of Hong Kong, Hong Kong/HK
  • 9 Oncology, Seoul National University, Seoul/KR
  • 10 Oncology, National Taiwan University Hospital, Taipei/TW
  • 11 Medicine, University of California, Los Angeles, Los Angeles/US
  • 12 Medical Oncology, Merck & Co., Inc., 07033 - Kenilworth/US
  • 13 Medicine, University of California, San Francisco, San Francisco/US
  • 14 Medical Oncology, Yale University School of Medicine, 06520 - New Haven/US


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Abstract 4799


KEYNOTE-495 is a randomized, open-label, phase II trial (NCT03516981) evaluating the clinical activity and safety of pembrolizumab (pembro)-based combination (combo) therapy in patients (pts) with treatment-naive, advanced NSCLC in biomarker-defined response groups. This biomarker-based approach is based on 2 validated, independent, next-generation biomarkers (T cell–inflamed gene expression profile [GEP] and tumor mutational burden [TMB]) and can help determine the differential efficacy of pembro-based combo therapy, based on the composite biomarker profile, and inform precision immunotherapy in the future.

Trial design

In this group-sequential, adaptive randomized trial, pts (N∼288) receive pembro 200 mg Q3W intravenously (IV) combined with MK-4280 (anti–LAG-3) 200 mg Q3W IV, lenvatinib (lenv) 20 mg PO QD, or MK-1308 (anti–CTLA-4) 25 mg Q6W IV for 35 cycles (∼2 years); pts in the lenv arm may receive lenv monotherapy until disease progression or toxicity. After biomarker screening, pts are assigned to 1 of 4 groups—TMBlowGEPlow, TMBhighGEPlow, TMBlowGEPhigh, and TMBhighGEPhigh—then randomized to 1 of 3 pembro-based regimens; adaptive design elements are used to adjust randomization based on objective responses. Eligible pts are ≥18 years of age with histologically or cytologically confirmed treatment-naive, advanced NSCLC; documented absence of EGFR and B-Raf mutations and ALK and ROS1 gene rearrangements; measurable disease per RECIST v1.1; and ECOG PS 0-1. Response is assessed by imaging Q9W for the first year and Q12W thereafter using RECIST v1.1. Primary end point is investigator-assessed objective response rate (RECIST v1.1). Secondary end points are progression-free survival, overall survival, and safety. Multiple interim analyses may be performed given the group-sequential design. Enrollment is ongoing.

Clinical trial identification

NCT03516981: Trial initiation, October 1, 2018.

Editorial acknowledgement

Holly C. Cappelli, PhD, and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA); funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.


Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.


M. Gutierrez: Advisory / Consultancy: Eli Lilly, Foundation One, Essanex, Guardant 360; Speaker Bureau / Expert testimony: Merck, BMS. M.D. Hellmann: Advisory / Consultancy: Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Janssen, Nektar, Syndax, Mirati, and Shattuck Labs; Shareholder / Stockholder / Stock options: Shattuck Labs; Research grant / Funding (institution): BMS; Travel / Accommodation / Expenses: AstraZeneca, BMS; Non-remunerated activity/ies, A patent has been filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx.: MSK. M.A. Gubens: Advisory / Consultancy: AbbVie, ARIAD, AstraZeneca, BMS, Roche/Genentech, Heron, Mersana, Novartis, Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene, Merck, Novartis; Research grant / Funding (institution): OncoMed, Roche. C. Aggarwal: Advisory / Consultancy: BMS, Celgene, Roche/Genentech, AstraZeneca. D.S.W. Tan: Honoraria (self): Novartis, Bayer, Boehringer Ingelheim, AstraZeneca, BMS, Roche, Takeda, Pfizer; Research grant / Funding (self): Novartis, Bayer, AstraZeneca, GSK, Pfizer; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Advisory / Consultancy: Blue Print Medicines, Celgene, Guardant Health. J.C. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, MSD, Pfizer, Novartis, BMS, Ono Pharmaceuticals ; Advisory / Consultancy: Merck Serono, Celgene, Merrimack, Yuhan Pharmaceuticals, Daiichi Sankyo, Hansoh Pharmaceuticals, Takeda Pharmaceuticals Blueprint Medicines. E.B. Garon: Research grant / Funding (self), Clinical trial funding: Merck, AstraZeneca, BMS. A. Basso: Full / Part-time employment: Merck . H. Ma: Full / Part-time employment: Merck . L. Fong: Research grant / Funding (self): Merck . A. Snyder: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck . J. Yuan: Full / Part-time employment: Merck . R.S. Herbst: Advisory / Consultancy: AbbVie, AstraZeneca, Biodesix, BMS, Eli Lilly, EMD Serano, Roche/Genentech, Heat Biologics, Junshi, Loxo Oncology Merck, Nektar, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum, Symphogen, Tesaro ; Research grant / Funding (self): AstraZeneca, Eli Lilly, Merck; Advisory / Consultancy, Scientific Advisory Boards: Neon Therapeutics, Infinity Pharmaceuticals, NextCure; Officer / Board of Directors: Junshi Pharmaceuticals. All other authors have declared no conflicts of interest.

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