144TiP - CheckMate 227: A randomized, open-label phase 3 trial of nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy i...

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic malignancies
Non-small-cell lung cancer
Therapy
Presenter Luis Paz-Ares
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors L. Paz-Ares1, J. Brahmer2, M.D. Hellmann3, M. Reck4, K. O'Byrne5, H. Borghaei6, W.J. Geese7, H. Lu7, F.E. Nathan7, S. Ramalingam8
  • 1Hospital Universitario Doce de Octubre, 28041 - Madrid/ES
  • 2Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
  • 3Memorial Sloan Kettering Cancer Center, New York/US
  • 4LungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf/DE
  • 5Cancer Services, Princess Alexandra Hospital, Brisbane/AU
  • 6Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 7Bristol-Myers Squibb, Princeton/US
  • 8Winship Cancer Institute, Emory University, Atlanta/US

Abstract

Background

Platinum-based chemotherapy is standard-of-care first-line therapy for most patients with advanced NSCLC, but the clinical benefit is modest. Although first-line nivolumab, an immune checkpoint inhibitor antibody, did not improve progression-free survival or overall survival (OS) versus chemotherapy in patients with advanced NSCLC and ≥5% programmed death-1 ligand 1 (PD-L1) expression, OS compared favorably with historical controls of first-line platinum-based chemotherapy. Combining nivolumab with chemotherapy in this setting may increase the durability of tumor responses and broaden the population of patients to derive benefit. In a multi-cohort phase 1 study (CheckMate 012) in chemotherapy-naïve patients with advanced NSCLC, nivolumab plus chemotherapy had promising clinical activity, regardless of tumor PD-L1 expression, and a manageable safety profile. CheckMate 227 is a 2-part, randomized, open-label phase 3 trial (NCT02477826), evaluating first-line nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in patients with advanced NSCLC.

Trial design

Part 1 of CheckMate 227, which has completed accrual, enrolled adult patients with stage IV/recurrent NSCLC, no prior systemic anticancer therapy, and assessment of PD-L1 expression at screening. Patients with ≥1% PD-L1 expression were randomized 1:1:1 to nivolumab, nivolumab plus ipilimumab, or chemotherapy arms; those with <1% PD-L1 expression were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy arms. In part 2, ∼480 previously untreated patients with advanced NSCLC, regardless of PD-L1 expression level, will be randomized 1:1 to receive histology-based platinum doublet chemotherapy alone or in combination with nivolumab. Part 2 of CheckMate 227, which is the focus of this presentation, allows for the evaluation of first-line nivolumab plus chemotherapy in a broad group of patients with advanced NSCLC across the PD-L1–expressing continuum.

Clinical trial identification

NCT02477826

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

L. Paz-Ares: Served as a medical advisor for the following companies: Lilly, Roche, MSD, BMS, Celgene, Pfizer, Boehringer-Ingelheim, Bayer, Clovis, and AstraZeneca. J. Brahmer: Received research grants and served as an uncompensated advisory board member for Bristol-Myers Squibb. M.D. Hellmann: Received grants from Genentech and Bristol-Myers Squibb. Received personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, and Janssen. M. Reck: Received consultant fees and served on speaker\'s bureau for the following companies: Roche, Lilly, Bristol-Myers Squibb, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. K. O\'Byrne: Received honoraria, speaker bureau and/or travel and registration support for national and international meetings from BMS, Boehringer-Ingelheim, Astrazeneca, Lilly Oncology, Novartis, MSD, Roche-Genentech and Pfizer. H. Borghaei: The institution has a clinical trial agreement w/BMS. Consultant/advisory board member for: BMS, Lilly, Genentech, Celgene, EMD-Serono, Merck, Pfizer, Trovagene, Millenium, & Boehringer-Ingelheim. Received grants from: Millenium, Merck, & Celgene. W.J. Geese, H. Lu: BMS Employee and stock holder. F.E. Nathan: BMS employee. S. Ramalingam: Served on ad hoc scientific advisory board meetings the following companies: Astra Zeneca, BMS, Boehringer Ingelheim, Celgene, Ariad, Amgen, Lilly, Merck, Genentech. Also received honoraria from BMS.