Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.

Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 9002)
F. Stephen Hodi, Mario Sznol, Harriet M. Kluger, David F. McDermott, Richard D. Carvajal, Donald P. Lawrence, Suzanne Louise Topalian, Michael B. Atkins, John D. Powderly, William Howard Sharfman, Igor Puzanov, David C. Smith, Philip D. Leming, Evan J. Lipson, Janis M. Taube, Robert Anders, Christine E. Horak, Georgia Kollia, Ashok Kumar Gupta, Jeffrey Alan Sosman; Dana-Farber Cancer Institute, Boston, MA; Yale Cancer Center, Yale School of Medicine, New Haven, CT; Beth Israel Deaconess Medical Center, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Massachusetts General Hospital Cancer Center, Boston, MA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Carolina BioOncology Institute, Huntersville, NC; Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN; University of Michigan, Ann Arbor, MI; The Christ Hospital Cancer Center, Cincinnati, OH; Bristol-Myers Squibb, Princeton, NJ; Vanderbilt University Medical Center, Nashville, TN

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Abstract Disclosures


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.