Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

Abstract

LBA9000^ Background: The humanized monoclonal IgG4 anti-PD-1 antibody MK-3475 has demonstrated durable antitumor activity in MEL and NSCLC. We evaluated MK-3475 efficacy and safety in a pooled analysis of 411 MEL pts. Methods: A nonrandomized cohort of ipilimumab-naive (IPI-N) and IPI-treated (IPI-T) pts treated with MK-3475 10 mg/kg Q2W, 10 mg/kg Q3W, or 2 mg/kg Q3W and randomized cohorts of IPI-N and IPI-T pts treated with 2 Q3W or 10 Q3W were included. Response was assessed every 12 wk by RECIST 1.1 by independent central review and by immune-related response criteria (irRC) by investigator. Results: 162 pts were treated at 2 Q3W, 192 at 10 Q3W, and 57 at 10 Q2W. 190 pts were IPI-N and 221 were IPI-T. As of the 10/18/2013 cutoff, all pts had ≥6 mo follow-up and >75% had ≥9 mo follow-up. Among the 365 pts with measurable disease at baseline, ORR by RECIST was 40% (95% CI 32%-48%) in IPI-N and 28% (95% CI 22%-35%) in IPI-T pts. Responses were durable (88% ongoing at analysis). Median PFS by RECIST was 24 wk in IPI-N and 23 wk in IPI-T pts. Median OS was not reached, with 1-y OS of 71% in all pts. Benefit was observed by both RECIST and irRC at all doses and schedules in IPI-N and IPI-T pts (Table). MK-3475 demonstrated activity in all major subgroups irrespective of ECOG PS, LDH levels, BRAFmutation, M stage, and number and type of prior therapy. Overall, 12% of pts experienced drug-related grade 3/4 AEs and 4% discontinued due to a drug-related AE. There were no drug-related deaths. Conclusions: MK-3475 showed durable responses and a manageable safety profile across dose and schedules in IPI-N and IPI-T MEL pts. The observed efficacy and safety suggest MK-3475 may be an appropriate treatment for all pts with MEL. Clinical trial information: NCT01295827. IPI-N IPI-T 2 Q3W n = 73 10 Q3W n = 76 10 Q2W n = 41 Total n = 190 2 Q3W n = 89 10 Q3W n = 116 10 Q2W n = 16 Total n = 221 RECIST ORR in pts with measurable disease, % 37 39 46 40 26 26 57 28 Median PFS, wk (95% CI) 36 (12-NR) 23 (12-36) 50 (14-NR) 24 (16-48) 22 (12-36) 17 (12-24) NR (12-NR) 23 (14-24) 24-wk PFS, % 52 46 57 51 45 40 67 44 irRC ORR, % 37 41 59 43 27 30 56 31 Median PFS, wk (95% CI) 36 (15-NR) 28 (13-NR) 84 (24-NR) 37 (24-84) 31 (22-48) 30 (24-NR) NR (12-NR) 36 (24-54) 24-wk PFS, % 57 52 61 56 57 56 73 58

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Affiliated Institutions

• University of California, Los Angeles US
• South Texas Accelerated Research Therapeutics US
• Institut Gustave Roussy FR
• Angeles Clinic and Research Institute US
• Moffitt Cancer Center US
• Merck & Co., Inc., Rahway, NJ, USA (United States) US
• Dana-Farber Cancer Institute US
• The University of Texas MD Anderson Cancer Center US
• The University of Sydney AU
• Westmead Hospital AU
• University of Pennsylvania US
• University of California, San Francisco US
• Memorial Sloan Kettering Cancer Center US
• Princess Margaret Cancer Centre CA
• Mayo Clinic in Arizona US
• Melanoma Institute Australia AU
• UPMC Hillman Cancer Center US

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