• Margaret K Callahan, Harriet Kluger, Michael A Postow, Neil H Segal, Alexander Lesokhin, Michael B Atkins, John M Kirkwood, Suba Krishnan, Rafia Bhore, Christine Horak, Jedd D Wolchok, and Mario Sznol.
• Margaret K. Callahan, Michael A. Postow, Neil H. Segal, Alexander Lesokhin, and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, NY; Harriet Kluger and Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, and Yale-New Haven Hospital, New Haven, CT; Michael B. Atkins, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; and Suba Krishnan, Rafia Bhore, and Christine Horak, Bristol-Myers Squibb, Princeton, NJ.
• J. Clin. Oncol. 2018 Feb 1; 36 (4): 391-398.

AbstractPurpose The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with previously treated or untreated advanced melanoma led to subsequent clinical development, including randomized trials. Here, we report long-term follow-up data from study CA209-004, including 3-year overall survival (OS). Patients and Methods Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for four doses, then NIVO plus IPI once every 12 weeks for eight doses. An expansion cohort (cohort 8) received concurrent NIVO 1 mg/kg plus IPI 3 mg/kg once every 3 weeks for four doses, followed by NIVO 3 mg/kg once every 2 weeks, which is the dose and schedule used in phase II and III studies and now approved for patients with unresectable or metastatic melanoma. Results Among all concurrent cohorts (N = 94) at a follow-up of 30.3 to 55.0 months, the 3-year OS rate was 63% and median OS had not been reached. Objective response rate by modified WHO criteria was 42%, and median duration of response was 22.3 months. Incidence of grade 3 and 4 treatment-related adverse events was 59%. The most common grade 3 and 4 treatment-related adverse events were increases in lipase (15%), alanine aminotransferase (12%), and aspartate aminotransferase (11%). One treatment-related death (1.1%) occurred in a patient who had multiorgan failure 70 days after the last dose of NIVO plus IPI. Conclusion This is the longest follow-up for NIVO plus IPI combination therapy in patients with advanced melanoma. The 3-year OS rate of 63% is the highest observed for this patient population and provides additional evidence for the durable clinical activity of immune checkpoint inhibitors in the treatment of advanced melanoma.

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