Randomized comparison of two doses of the anti-PD-1 monoclonal antibody MK-347 for ipilimumab-refractory (IPI-R) and IPI-naive (IPI-N) melanoma (MEL)

Omid Hamid, Caroline Robert, Antoni Ribas, Jedd D. Wolchok, F. Stephen Hodi, Richard Kefford, Anthony M. Joshua, Wen-Jen Hwu, Tara C. Gangadhar, Arnita Patnaik, Peter Hersey, Jeffrey S. Weber, Richard Wayne Joseph, Kevin Gergich, Xiaoyun (Nicole) Li, Patrick Chun, Scot Ebbinghaus, Soonmo Peter Kang, Adil Daud

Research output: Contribution to journalMeeting abstract

Abstract

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.
Original languageEnglish
Pages (from-to)3000-3000
Number of pages1
JournalJournal of Clinical Oncology
Volume32
Issue number15
DOIs
Publication statusPublished - 20 May 2014
Externally publishedYes
Event50th Annual Meeting of the American-Society-of-Clinical-Oncology - Chicago, United States
Duration: 30 May 20143 Jun 2014

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