1088PD - Long-term survival of ipilimumab-naïve patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1; BMS-936558, ONO-4538) in a ph...

Date 29 September 2014
Event ESMO 2014
Session Melanoma and other skin tumours
Topics Immunotherapy
Skin Cancers
Presenter David McDermott
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors D.F. McDermott1, H. Kluger2, M. Sznol3, R. Carvajal4, D. Lawrence5, S.L. Topalian6, M.B. Atkins7, J.D. Powderly8, W.H. Sharfman9, I. Puzanov10, D. Smith11, P.D. Leming12, E. Lipson6, J.M. Taube13, R.A. Anders14, C. Horak15, G. Kollia16, J.A. Sosman17, F.S. Hodi18
  • 1Division Of Hematology/oncology, Beth Israel Deaconess Med. Center Dept. Radiation Oncology, 02215 - Boston/US
  • 2Yale Cancer Center, Yale University School of Medicine and Smilow Cancer Center, New Haven/US
  • 3Yale Cancer Center, Yale Comprehensive Cancer Center(Smilow Cancer Hospital at Yale-New Haven), New Haven/US
  • 4Ludwig Center, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 5Center For Melanoma, Massachusetts General Hospital Cancer Center, Boston/US
  • 6The Sidney Kimmel Comprehensive Cancer Center, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
  • 7Internal Medicine, Georgetown Lombardi Comprehensive Cancer Center, Washington DC/US
  • 8Oncology, Carolina Bio-Oncology Institute, Huntersville/US
  • 9Cancer Center At Johns Hopkins, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
  • 10Division Of Hematology-oncology, Vanderbilt University Medical Center, 37232-6307 - Nashville/US
  • 11Department Of Internal Medicine, University of Michigan, Ann Arbor/US
  • 12Hematology/oncology, The Christ Hospital, Cincinnati/US
  • 13Melanoma Program, Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore/US
  • 14Pathology/oncology, The Johns Hopkins Hospital, Baltimore/US
  • 15Clinical Biomarkers - Oncology, Bristol-Myers Squibb, Princeton/US
  • 16Biostatistics And Data Management, Bristol-Myers Squibb, Princeton/US
  • 17Haematology/ Oncology, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 18Medical Oncology, Dana-Farber Cancer Institute, Boston/US




Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, is active and tolerable in pts with advanced MEL (Topalian et al. NEJM 366:2443, 2012). We report long-term clinical activity, response duration off-therapy, tumor PD-1 ligand (PD-L1) expression associated with survival endpoints, and 3-yr overall survival (OS) for the MEL pts in this phase 1 trial.


Previously treated pts with advanced MEL and no prior ipilimumab therapy received nivolumab 0.1, 0.3, 1, 3 or 10 mg/kg IV Q2W for ≤96 wks and were evaluated for OS and progression-free survival (PFS). Tumor cell surface expression of PD-L1 was retrospectively assessed in archival pretreatment specimens by a Dako immunohistochemistry assay, with PD-L1+ defined as ≥5% tumor cells expressing this marker.


From 2008–2012, 107 MEL pts initiated treatment with nivolumab: 25% had ≥3 prior therapies. One-, 2- and 3-yr OS rates were 63%, 48% and 41%, respectively. For the 33/107 (31%) pts with objective responses (OR; RECIST), median response duration was 22.9 months. Twenty-four OR pts stopped nivolumab for reasons other than disease progression; 11 (46%) maintained responses for ≥24 wks off drug (range: 24, 56+ wks). Four (4%) additional pts had unconventional “immune-related” responses; overall survival for these pts was 21.1, 28.6 + , 43.1+ and 48.0+ months as of September 2013. In a subset of 41/107 pts with available tumor samples, median OS for pts with PD-L1+ (n = 18) and PD-L1– (n = 23) tumors was not reached and 12.5 months, respectively; median PFS was 9.1 and 1.9 months, respectively. Safety has been previously reported (Topalian et al. J Clin Oncol 32:1020, 2014).


In pts with advanced MEL, nivolumab demonstrated notable 2- and 3-yr OS rates, durable responses with several persisting following discontinuation of therapy, and an acceptable safety profile. Additional analyses will be presented on the correlation between key pt characteristics and response to nivolumab. Ongoing phase 3 trials are further evaluating nivolumab for MEL pts and will also explore the role of PD-L1 as a potential predictive biomarker for nivolumab activity.


D.F. McDermott: Consultant advisor, BMS advisory board; Research Funding BMS; M. Sznol: Paid consultant and scientific advisory board-Bristol-Myers Squibb, Genentech/Roche, MedImunne, Amgen, Nektar, Symphogen, Merus, Amphivena, NeoStem, Anaeropharma, BeiGene, Kyowa-Kirin, Immune Design, Lion Biotechnologies, Seattle Genetics; R. Carvajal: Consultant- Aura Biosciences; S.L. Topalian: Consultant-BMS(uncompensated), Jounce Therapeutics (comp.), Sanofi (comp.); Stock options: Compugen, Amplimmune, NexImmune, Jounce Therapuetics; Research funding BMS; Other remuneration-BMS and Amplimmune Inc., patent royalties through Johns Hopkins Univ; M.B. Atkins: Consultant advisor, honoraria- BMS; J.D. Powderly: Employment-Biologics Human Application Lab; Consultant advisor-BMS, Genetech, Amplimmune, Merck; Honoraria-BMS; Research Funding-BMS, Genetech, Amplimmune, Merck, AstraZeneca; Other Rumuneration-BMS Speakers Bureau and Advisory Boards; W.H. Sharfman: Consultant advisor, honoraria-MerckM; D.C. Smith: Research funding-BMS; J.M. Taube: Consultant advisor, research funding-BMS; R.A. Anders: Research Funding BMS; C. Horak: BMS-employee, stock; G. Kollia: BMS-employee, stock; J.A. Sosman: Consultant advisor-BMS; Honoraria-Glaxo Smith Kline, Amgen; Research funding-BMS, Novartis, Glaxo Smith Kline; F.S. Hodi: Consultant advisor BMS-uncompensated. All other authors have declared no conflicts of interest.