Clinical response, PFS and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) versus IPI monotherapy in CheckMate 069 study
1Dana-Farber Cancer Institute, Boston, MA, USA,2Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA,3J. Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA,4New York University, Perlmutter Cancer Center, New York, NY, USA,5Gustave, Roussy and Paris-Sud University, Villejuif-Paris-Sud, France,6Huntsman Cancer Institute, Salt Lake City, UT, USA,7Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA,8Washington University, St. Louis, MO, USA,9Institut Universitaire du Cancer, Toulouse, France,10Greenville Health System, Greenville, SC, USA,11St. Lukes Cancer Center, Bethlehem, PA, USA,12University of New Mexico, Albuquerque, NM, USA,13Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA,14California Pacific Melanoma Center, San Francisco, CA, USA,15Duke University, Durham, NC, USA,16Oregon Health & Science University, Portland, OR, USA,17Bristol-Myers Squibb, Princeton, NJ, USA,18Bristol-Myers Squibb, Wallingford, CT, USA
Combined blockade of T-cell checkpoints by NIVO and IPI demonstrated a high objective response rate (ORR), promising overall survival and a manageable safety profile in pts with advanced MEL. We report efficacy and safety of NIVO + IPI versus IPI alone in treatment-naïve pts with advanced MEL in a phase II study.
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.
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 vs 4.7 months, respectively (P=0.0012). Higher ORR was observed for NIVO + IPI versus IPI in poor prognostic pt subgroups: elevated baseline LDH (53% vs 0%); M1c stage disease (62% vs 25%). Similar ORR and PFS 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 and generally manageable.
NIVO + IPI significantly improved ORR and PFS compared with IPI alone, had a manageable safety profile across pt subgroups, and provided a favorable risk-benefit ratio in treatment-naïve pts with advanced MEL.