Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer

作者：Suzanne L. Topalian, F. Stephen Hodi, Julie R. Brahmer, Scott Gettinger, David C. Smith, David F. McDermott, John D. Powderly, Richard D. Carvajal, Jeffrey A. Sosman, Michael B. Atkins, Philip D. Leming, David R. Spigel, Scott Antonia, Leora Horn, Charles G. Drake, Drew M. Pardoll, Lieping Chen, William H. Sharfman, Robert A. Anders, Janis M. Taube, Tracee L. McMiller, Haiying Xu, Alan J. Korman, Maria Jure–Kunkel, Shruti Agrawal, D. G. McDonald, Georgia Kollia, Ashok Gupta, Jon M. Wigginton, Mario Sznol · 发表于：New England Journal of Medicine · 年份：2012 · DOI：10.1056/nejmoa1200690 · 被引用次数：12806 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、CAR-T cell therapy research

BACKGROUND: Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. METHODS: We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. RESULTS: A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the r...