Abstract CT001: Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial
Authors: Hodi F. Stephen , Kluger Harriet , Sznol Mario , Carvajal Richard , Lawrence Donald , Atkins Michael , Powderly John , Sharfman William , Puzanov Igor , Smith David , Leming Philip , Lipson Evan , Taube Janis , Anders Robert , Horak Christine , Jiang Joel , McDermott David , Sosman Jeffrey , Brahmer Julie , Pardoll Drew , Topalian Suzanne 
Published: July 2016

Abstract
Background: In previously treated MEL patients (pts), the results of an early phase I trial with NIVO monotherapy (CA209-003) demonstrated tumor responses that were durable even after treatment discontinuation (Topalian et al. J Clin Oncol 2014;32:1020). We report extended follow-up with 5-year overall survival (OS) data from this study.
Methods: IPI-naïve pts (N = 107) who had received 1-5 prior systemic therapies for MEL were treated with NIVO (0.1, 0.3, 1, 3, or 10 mg/kg) every 2 weeks for ?96 weeks. Pts were followed for OS, progression-free survival (PFS), long-term safety, and response duration after discontinuing NIVO treatment. Pts began treatment in October 2008, and current data were analyzed in October 2015 with a minimum follow-up of 45 months (time from when the last pt received his or her first dose of NIVO).
Results: Median age of the pts was 61 years, 67% were male, 97% had an ECOG performance status of 0 or 1, 62% had received ?2 prior systemic therapies, and 36% had elevated lactate dehydrogenase levels at baseline. In all 107 pts, the 60-month OS rate was 34% (95% confidence interval [CI]: 25-43) and median OS was 17.3 months (95% CI: 12.5-37.8) (Table). OS rates appeared to plateau at ∼48 months, although further follow-up is needed. Similar results were observed with NIVO at 3 mg/kg, the currently approved monotherapy dose (Table). At the last timepoint for tumor assessment, PFS rates at 30 months were 18.6% and 25.7% for all pts and those who received NIVO at 3 mg/kg, respectively.
Conclusions: This analysis represents the longest survival follow-up of pts who received anti-PD-1 therapy in a clinical study. In this heavily pretreated population of MEL pts, these results suggest durable, long-term survival following NIVO monotherapy, with 34% of pts alive at 5 years. Characteristics of long-term survivors and updated safety data will also be presented. OS ratesNIVO 3 mg/kg (n=17)All Patients (N=107)OS rate, % (95% CI)*12-month64.7 (37.7-82.3)62.7 (52.6-71.2)24-month47.1 (23.0-68.0)48.0 (38.1-57.2)36-month41.2 (18.6-62.6)42.1 (32.4-51.4)48-month35.3 (14.5-57.0)34.8 (25.7-44.1)60-month35.3 (14.5-57.0)33.6 (24.6-42.9)Median OS, months (95% CI)20.3 (7.2-NR)17.3 (12.5-37.8)*Based on Kaplan-Meier estimates.NR, not reached.
Citation Format: F. Stephen Hodi, Harriet Kluger, Mario Sznol, Richard Carvajal, Donald Lawrence, Michael Atkins, John Powderly, William Sharfman, Igor Puzanov, David Smith, Philip Leming, Evan Lipson, Janis Taube, Robert Anders, Christine Horak, Joel Jiang, David McDermott, Jeffrey Sosman, Julie Brahmer, Drew Pardoll, Suzanne Topalian. Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT001.