Randomized comparison of two doses of the anti-PD-1 monoclonal antibody MK-3475 for ipilimumab-refractory (IPI-R) and IPI-naive (IPI-N) melanoma (MEL).

Abstract

3000 Background: MK-3475 has shown durable antitumor activity in MEL across multiple doses and schedules. We compared the efficacy and safety of 2 MK-3475 doses in MEL patients (pts). Methods: In separate cohorts, IPI-N and IPI-R pts were randomized 1:1 to MK-3475 2 or 10 mg/kg every 3 wk (2 Q3W or 10 Q3W). IPI-N pts received ≤2 prior systemic therapies. IPI-R pts had any number of prior therapies and unequivocal or confirmed PD per immune-related response criteria (irRC) after ≥2 IPI doses; all BRAF-mutant pts were previously treated with BRAF inhibitors. Primary endpoint was ORR assessed by RECIST 1.1 every 12 wk by independent central review. Investigator-assessed response by irRC was also obtained. Results: A total of 276 pts were randomized (103 IPI-N [2 Q3W, n = 51; 10 Q3W, n = 52] and 173 IPI-R [2 Q3W, n = 89; 10 Q3W, n = 84]. In both cohorts, treatment arms were well balanced for known prognostic factors. As of the 10/18/2013 cutoff, all IPI-N and 47% of IPI-T pts had ≥9 mo of follow-up. Among evaluable pts, no significant differences in ORR by RECIST were observed between doses in IPI-N (33% vs 40%) or IPI-R (26% vs 26%) pts. By RECIST, response duration ranged from 6+ wk to 39+ wk in both cohorts (median not reached), with ~90% of responses ongoing. PFS by RECIST was similar between doses. The safety profile was generally similar between pts treated with 2 Q3W and 10 Q3W. There were no drug-related deaths. Conclusions: MK-3475 2 mg/kg Q3W and 10 mg/kg Q3W provided similar efficacy and safety in both IPI-N pts and IPI-R pts. Treatment was well tolerated with acceptable toxicity profile. The high ORR provided by MK-3475 comes with long durability in both IPI-N and IPI-R MEL. Clinical trial information: NCT01295827. RECIST 1.1 irRC 2 Q3W 10 Q3W 2-sided P 2 Q3W 10 Q3W 2-sided P IPI-N ORR, % (95% CI) 33 (20-49) 40 (26-56) .4835 39 (26-54) 40 (27-55) .9040 Response duration, wk, range 7+ – 36+ 6+ – 39+ — 12+ – 42+ 10+ – 39+ — Median PFS, wk(95% CI) 27 (12-NR) 23 (12-48) — 36 (13-NR) 26 (12-NR) — 24-wk PFS, % 51 48 — 60 50 — IPI-R ORR, % (95% CI) 26 (17-37) 26 (17-38) .9558 27 (18-37) 32 (22-43) .4568 Response duration, wk, range 6+ – 37+ 8+ – 37+ — 12+ – 42+ 4+ – 37+ — Median PFS, wk (95% CI) 22 (12-36) 14 (12-24) — 31 (22-48) 35 (24-NR) — 24-wk PFS, % 45 37 — 57 57 —