Clinical response, progression-free survival (PFS), and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) vs IPI monotherapy in CheckMate 069 study.

Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 9004)
F. Stephen Hodi, Michael Andrew Postow, Jason Alan Chesney, Anna C. Pavlick, Caroline Robert, Kenneth F. Grossmann, David F. McDermott, Gerald P. Linette, Nicolas Meyer, Jeffrey K. Giguere, Sanjiv S. Agarwala, Montaser F. Shaheen, Marc S. Ernstoff, David R. Minor, April Salama, Matthew Hiram Taylor, Patrick Alexander Ott, Christine E. Horak, Paul Gagnier, Jedd D. Wolchok; Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; J. Graham Brown Cancer Center, University of Louisville, Louisville, KY; New York University, Perlmutter Cancer Center, New York, NY; Gustave, Roussy and Paris-Sud University, Villejuif-Paris-Sud, France; Huntsman Cancer Institute, Salt Lake City, UT; Beth Israel Deaconess Medical Center, Boston, MA; Washington University, St. Louis, MO; Institut Universitaire du Cancer, Toulouse, France; NCORP of the Carolinas, Greenville, SC; St. Luke’s Cancer Center, Bethlehem, PA; University of New Mexico, Albuquerque, NM; Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH; California Pacific Melanoma Center, San Francisco, CA; Duke University, Durham, NC; Oregon Health & Science University, Portland, OR; Bristol-Myers Squibb, Princeton, NJ; Bristol-Myers Squibb, Wallingford, CT

Abstract Disclosures


Background: Combined blockade of T-cell checkpoints by NIVO and IPI demonstrated a high objective response rate (ORR), promising overall survival (OS), and a manageable safety profile in pts with advanced MEL in a phase I study, based on which an appropriate dose was selected for registrational trials. We report efficacy and safety of the NIVO + IPI combination vs IPI alone in treatment-naïve pts with advanced MEL, including pts with poor prognostic factors, in a phase II study. Methods: Pts (N = 142) with metastatic or unresectable MEL were randomized 2:1 to receive IPI 3 mg/kg combined with either NIVO 1 mg/kg or placebo Q3W × 4, followed by NIVO 3 mg/kg or placebo Q2W until disease progression or unacceptable toxicity. The primary endpoint was ORR in BRAF wild-type (WT) pts. Secondary and exploratory objectives included PFS in BRAF WT pts, ORR and PFS in BRAF V600 mutation-positive (MT) pts, and safety. Results: In BRAF WT pts (n = 109), ORR was 60% (43/72) for NIVO + IPI; 11% (4/37) for IPI alone (P < 0.0001); complete responses were reported in 12 (17%) and 0 pts, respectively. Median PFS was 8.9 months for the combination vs 4.7 months for IPI alone (P = 0.0012). Higher ORR was observed for NIVO + IPI vs IPI in predefined pt subgroups with poor prognostic factors, such as elevated baseline LDH (53% vs 0%) and M1c stage disease (62% vs 25%). Similar ORR and PFS results were observed in 33 BRAF MT pts. Grade 3–4 drug-related adverse events (AEs) were reported in 51% of pts receiving NIVO + IPI vs 20% for IPI alone. The safety profile of NIVO + IPI was similar across pt subgroups, including age. Select AEs related to the combination regimen were consistent with phase I reports and most resolved with immunosuppressive medication ( > 83% across organ categories) with the exception of endocrinopathies. Updated results from a planned data analysis in March 2015 will be presented. Conclusions: NIVO + IPI significantly improved ORR and PFS compared with IPI alone and had a manageable safety profile. The efficacy and safety of the combination was similar across pt subgroups and provided a favorable risk-benefit ratio in treatment-naïve pts with advanced MEL. Clinical trial information: NCT01927419