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9002 Background: We have shown that nivolumab, a fully human IgG4 PD-1 immune-checkpoint inhibitor antibody, is tolerable and active in pts with advanced solid tumors in a large phase I trial (Topalian et al. N Eng J Med 366:2443-54, 2012). For the MEL pts in this trial, we report long-term clinical activity, pts’ response off therapy, tumor PD-1 ligand (PD-L1) expression associated with survival endpoints, and for the first time, 3-y overall survival (OS). Methods: Previously treated advanced MEL pts with no prior ipilimumab therapy received nivolumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) Q2Wk for ≤96 wk and were evaluated for OS and progression-free survival (PFS). PD-L1 tumor cell membrane expression was retrospectively assessed in archival specimens by a Dako immunohistochemistry assay with ≥5% tumor cells designated as PD-L1(+). Results: From 2008-2012, 107 MEL pts initiated treatment with nivolumab; 25% had ≥3 prior therapies. Across doses, the 2- and 3-y OS rates were 48 and 41%, respectively (Table). For the 34/107 (32%) pts with objective responses (OR; RECIST), median response duration was 22.9 mo. Twenty-four OR pts stopped nivolumab for reasons other than disease progression; 11 (46%) maintained responses for ≥24 wk off drug (range: 24, 56+ wk). Four (4%) pts had unconventional “immune-related” responses. In a subset of pts with evaluable tumor samples (41/107), pts with PD-L1(+) and (–) tumors (n=18 and 23, respectively) had median OS of not reached and 12.5 mo; median PFS was 9.1 mo and 1.9 mo. Safety has been previously reported (Sznol et al. J Clin Oncol 31:abs CRA9006, 2013). Conclusions: In advanced MEL pts, nivolumab demonstrated favorable 2- and 3-y OS rates, durable responses with a number persisting off therapy, and an acceptable safety profile. Additional analyses will be presented by pts’ characteristics across the full population, the long-term survival subgroup, and the PD-L1(+/–) tumor subgroups. Ongoing phase III trials are further evaluating nivolumab for MEL pts and PD-L1 as a potential predictive biomarker for response to nivolumab. Clinical trial information: NCT00730639. OS rate* n=107 % (95% CI) Pts at risk 1 y 63 (53, 71) 63 2 y 48 (38, 57) 44 3 y 41 (31, 51) 22 *September 2013 analysis.
Hodi et al. (Tue,) studied this question.