Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).

Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr CRA9006^)
Mario Sznol, Harriet M. Kluger, F. Stephen Hodi, 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, Jon M. Wigginton, Georgia Kollia, Ashok Kumar Gupta, Jeffrey Alan Sosman; Yale Cancer Center, New Haven, CT; Yale University, New Haven, CT; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital Cancer Center, Boston, MA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC; Carolina BioOncology Institute, Huntersville, NC; Vanderbilt University Medical Center, Nashville, TN; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Bristol-Myers Squibb, Princeton, NJ

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Abstract Disclosures


Background: The monoclonal antibody nivolumab blocks PD-1, an inhibitory immune checkpoint receptor expressed by activated T cells. Pts with previously treated MEL or other tumors received nivolumab IV Q2W during dose escalation and/or cohort expansion in a phase I trial (Topalian et al., NEJM 2012;366:2443). Methods: Pts received ≤12 cycles (4 doses/cycle) of treatment until discontinuation criteria were met. Cohorts of MEL pts were expanded at 0.1, 0.3, 1, 3, and 10 mg/kg. We report overall survival data and long-term safety and response data from the MEL pts treated on this study. Results: 107 MEL pts received nivolumab as of July 2012. 103/107 pts (97%) were ECOG PS ≤1 and approximately 25% received ≥3 prior therapies. Median OS was 16.8 months across doses and 20.3 months at the 3 mg/kg dose selected for phase III trials. 44% and 40% of pts were alive at 2 and 3 yrs (Table). ORs were observed at all doses (highest at 3 mg/kg) (Table). Of 29 responders who initiated treatment ≥1 year prior to data analysis, 16 had responses lasting ≥1 year. Drug-related AEs (any grade) occurred in 82% of pts, with Gr 3-4 drug-related AEs in 21% of pts; the most common included lymphopenia (3%), fatigue, and increased lipase (2%). Gr 3-4 drug-related diarrhea (2%), endocrine disorders (2%), and hepatitis (1%) was observed. No Gr ≥3 drug-related pneumonitis was observed in the MEL cohort. Conclusions: In this large cohort of pretreated MEL pts, nivolumab produced durable OS and responses with an acceptable safety profile. OS compares favorably with historical data. Data updated as of Feb 2013 will be reported. Phase III registration trials have been initiated. Clinical trial information: NCT00730639.

na ORR, n (%) Median OS
months (95% CI)
All 106 33 (31) 16.8 (12.5 – NR)
0.1 17 6 (35) NR (8.6 – NR)
0.3 18 5 (28) 12.5 (7.7 – NR)
1 34 11 (32) NR (8.2 – NR)
3 17 7 (41)b 20.3 (8.2 – NR)
10 20 4 (20) 10.5 (7.2 – NR)
OS ratec % (95% CI) Pts at risk, n
1 Yr 61% (52-71) 50
2 Yr 44% (33-56) 24
3 Yr 40% (29-52) 1

a Response-evaluable pts on study ≥6 mo. b 1 CR. cAll doses. OS estimates after 1 year reflect heavy censoring and shorter follow-up for pts enrolling later in the study. NR = not reached.