Long-term survival of ipilimumab-naïve patients with advanced melanoma (MEL) treated with nivolumab (anti-Programmed Death-1; anti-PD-1; BMS-936558; ONO-4538) in a phase I trial. — ASN Events
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  3. Long-term survival of ipilimumab-naïve patients with advanced melanoma (MEL) treated with nivolumab (anti-Programmed Death-1; anti-PD-1; BMS-936558; ONO-4538) in a phase I trial.

Long-term survival of ipilimumab-naïve patients with advanced melanoma (MEL) treated with nivolumab (anti-Programmed Death-1; anti-PD-1; BMS-936558; ONO-4538) in a phase I trial. (#378)

Stephen Hodi 1 , Mario Sznol 2 , Harriet M Kluger 2 , David F McDermott 3 , Richard D Carvajal 4 , Donald P Lawrence 5 , Suzanne L Topalian 6 , Michael B Atkins 7 , John D Powderly 8 , William H Sharfman 5 , Igor Puzanov 9 , David C Smith 10 , Philip D Leming 11 , Evan J Lipson 6 , Janis M Taube 6 , Robert A Anders 6 , Christine E Horak 12 , Georgia Kollia 12 , Ashok Gupta 12 , Jeffrey A Sosman 9
  1. Dana-Farber Cancer Institute, Boston, MA, USA
  2. Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT, USA
  3. Beth Israel Deaconess Medical Center, Boston, MA, USA
  4. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  5. Massachusetts General Hospital Cancer Center, Boston, MA, USA
  6. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
  7. Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA
  8. Carolina BioOncology Institute, Huntersville, NC, USA
  9. Vanderbilt University Medical Center, Nashville, TN, USA
  10. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
  11. Christ Hospital Cancer Center, Cincinnati, Ohio, USA
  12. Bristol-Myers Squibb, Princeton, NJ, USA

Aims: Nivolumab, a fully human immunoglobulin G4 PD-1 immune-checkpoint inhibitor antibody, is tolerable and active in patients with advanced solid tumors. In this trial, long-term clinical activity, response off therapy, association of tumor PD-1 ligand 1 (PD-L1) expression with survival endpoints, and 3-year overall survival (OS) were investigated in patients with advanced MEL.

Methods: 107 previously treated ipilimumab-naïve advanced MEL patients received nivolumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) every fortnight for ≤96 weeks and were evaluated for OS and progression-free survival (PFS). Tumour cell PD-L1 expression was assessed by a Dako immunohistochemistry assay.

Results: Among patients who initiated treatment with nivolumab, 25% had ≥3 prior therapies. Across doses, 1-, 2- and 3-year OS (95% CI) rates were 63% (53, 71), 48% (38, 57) and 41% (31, 51), respectively; and numbers of patients at risk were 63, 44 and 22, respectively. Thirty-four patients demonstrated objective responses by RECIST, 24 of whom stopped nivolumab for reasons other than disease progression. Of those 11 maintained responses for ≥24 weeks off drug (range: 24, 56+ weeks); and 4 had unconventional “immune-related” responses.
Median response duration was 22.9 months. In a subset of patients with evaluable tumor samples (41/107), patients with PD-L1(+) (i.e. ≥ 5% on tumour cells) and (–) tumours (n=18 and 23, respectively) had median OS of not reached and 12.5 months, respectively; median PFS was 9.1 months and 1.9 months, respectively. Safety was previously reported.

Conclusions: In advanced MEL patients, nivolumab demonstrated favorable 2- and 3-year OS rates, durable responses with a number persisting off therapy, and an acceptable safety profile. Additional analyses will be presented by patients’ characteristics across the full population, long-term survival subgroup, and PD-L1(+/–) tumor subgroups. Ongoing phase III trials are further evaluating nivolumab in MEL and PD-L1 as a potential predictive biomarker for response.

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