195TiP - Pembrolizumab (MK-3475) versus platinum-based chemotherapy for PD-L1+ NSCLC in a phase 3, randomized, open-label study: KEYNOTE-042

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer agents
Immunotherapy
Non-Small Cell Lung Cancer
Therapy
Biological Therapy
Presenter Tony S.K. Mok
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors T.S.K. Mok1, Y. Wu2, S. Sadowski3, J. Zhang4, R. Rangwala3, D. Kush3, G. de Lima Lopes5
  • 1Clinical Oncology, The Chinese University of Hong Kong, N.T. - Hong Kong/HK
  • 2Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangdong/CN
  • 3Clinical Oncology, Merck & Co., Inc., Kenilworth/US
  • 4Bards, Merck & Co., Inc., Kenilworth/US
  • 5Oncology, Centro Paulista de Oncologia e HCor Onco, members of the Oncoclínicas do Brasil Group, São Paulo/BR

Abstract

Background

Tumors use the PD-1 pathway to suppress immune responses. The anti-PD-1 monoclonal antibody pembrolizumab (pembro) showed a manageable safety profile and promising antitumor activity in pts with treatment-naive NSCLC enrolled in the phase 1b KEYNOTE-001 study. KEYNOTE-042 (NCT02220894) is a randomized, open-label, international, phase 3 study comparing the efficacy and safety of pembro with those of platinum-doublet chemotherapy, the standard therapy for treatment-naive NSCLC lacking ALK translocations or EGFR-sensitizing mutations, as first-line therapy for PD-L1+ advanced NSCLC.

Trial design

Pts with advanced NSCLC w/o EGFR-sensitizing mutations or ALK translocations and no prior systemic chemotherapy are eligible if they have PD-L1 expression in ≥1% of tumor cells and ECOG PS 0–1. Pts are randomized 1:1 to receive 200 mg pembro Q3W or investigator's choice of carboplatin AUC 5 or 6 + paclitaxel 200 mg/m2 Q3W or carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 Q3W. Randomization is stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), region (East Asia vs non-East Asia), and PD-L1 expression (staining in ≥50% of tumor cells [tumor proportion score (TPS) ≥50%] vs [TPS 1%-49%] as assessed by IHC). Pembro will continue for 35 cycles or until progression, intolerable toxicity, or investigator decision; treatment may continue beyond initial radiographic disease progression in eligible pts. Discontinuation of pembro is permitted for pts who have CR confirmed ≥4 wk after initial observation. Chemotherapy will be given for a maximum of 6 cycles and may be followed by optional pemetrexed 500 mg/m2 Q3W maintenance therapy in pts with nonsquamous histology. AEs will be collected throughout the study and for 30 d (90 d for serious AEs) thereafter and graded per NCI CTCAE v4.0. Response will be assessed every 9 wk per RECIST v1.1 by central independent radiologists' review. Pts will be followed for survival every 2 mo. Primary endpoint is OS in the PD-L1 TPS ≥50% stratum and in all pts; secondary endpoints are PFS in the TPS ≥50% stratum and in all pts, and safety and tolerability. Enrollment is ongoing and will continue until ∼1240 pts have enrolled.

Clinical trial identification

NCT02220894 (Release date 19 August 2014)

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ USA

Funding

Merck & Co., Inc., Kenilworth, NJ USA

Disclosure

T. Mok: Speaker Bureau, Honoraria, Ad Board: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Janssen, Clovis Oncology, GSK, Novartis Speaker Bureau, Honoraria: Amgen Stock Shareholder: Sanomics Ltd Ad Board for: Merck Serono, BioMarin, SFJ Pharmaceutical. Y.-L. Wu: Speaker Fees from: AstraZeneca, Roche, Eli Lilly, Pfizer and Sanofi. S. Sadowski, J. Zhang, R. Rangwala, D. Kush: Employee of Merck & Co., Inc. G. de Lima Lopes: Research funding and honoraria from: Roche, Sanofi Aventis, Eli Lilly, Merck Serono, Merck Sharp and Dhome, BMS, Pfizer, Fresenius Kabi, Astra Zeneca.