Scott N Gettinger1, Leora Horn2, Leena Gandhi2, David R Spigel2, Scott J Antonia2, Naiyer A Rizvi2, John D Powderly2, Rebecca S Heist2, Richard D Carvajal2, David M Jackman2, Lecia V Sequist2, David C Smith2, Philip Leming2, David P Carbone2, Mary C Pinder-Schenck2, Suzanne L Topalian2, F Stephen Hodi2, Jeffrey A Sosman2, Mario Sznol2, David F McDermott2, Drew M Pardoll2, Vindira Sankar2, Christoph M Ahlers2, Mark Salvati2, Jon M Wigginton2, Matthew D Hellmann2, Georgia D Kollia2, Ashok K Gupta2, Julie R Brahmer2. 1. Scott N. Gettinger and Mario Sznol, Yale Cancer Center, New Haven, CT; Leora Horn, David P. Carbone, and Jeffrey A. Sosman, Vanderbilt University Medical Center; David R. Spigel, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Leena Gandhi, David M. Jackman, and F. Stephen Hodi, Dana-Farber Cancer Institute; Rebecca S. Heist and Lecia V. Sequist, Massachusetts General Hospital Cancer Center; David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Scott J. Antonia and Mary C. Pinder-Schenck, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Naiyer A. Rizvi, Richard D. Carvajal, and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; David C. Smith, University of Michigan, Ann Arbor, MI; Philip Leming, Christ Hospital Cancer Center, Cincinnati, OH; Suzanne L. Topalian, Drew M. Pardoll, and Julie R. Brahmer, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; and Vindira Sankar, Christoph M. Ahlers, Mark Salvati, Jon M. Wigginton, Georgia D. Kollia, and Ashok K. Gupta, Bristol-Myers Squibb, Princeton, NJ. scott.gettinger@yale.edu. 2. Scott N. Gettinger and Mario Sznol, Yale Cancer Center, New Haven, CT; Leora Horn, David P. Carbone, and Jeffrey A. Sosman, Vanderbilt University Medical Center; David R. Spigel, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Leena Gandhi, David M. Jackman, and F. Stephen Hodi, Dana-Farber Cancer Institute; Rebecca S. Heist and Lecia V. Sequist, Massachusetts General Hospital Cancer Center; David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Scott J. Antonia and Mary C. Pinder-Schenck, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Naiyer A. Rizvi, Richard D. Carvajal, and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; David C. Smith, University of Michigan, Ann Arbor, MI; Philip Leming, Christ Hospital Cancer Center, Cincinnati, OH; Suzanne L. Topalian, Drew M. Pardoll, and Julie R. Brahmer, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; and Vindira Sankar, Christoph M. Ahlers, Mark Salvati, Jon M. Wigginton, Georgia D. Kollia, and Ashok K. Gupta, Bristol-Myers Squibb, Princeton, NJ.
Abstract
PURPOSE: Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. PATIENTS AND METHODS: Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. RESULTS: Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. CONCLUSION: Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.
PURPOSE: Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial. PATIENTS AND METHODS: Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. RESULTS: Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. CONCLUSION:Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.
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