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).

Developmental Therapeutics - Immunotherapy
Session Type and Session Title: 
Oral Abstract Session, Developmental Therapeutics - Immunotherapy
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 3000)
Omid Hamid, Caroline Robert, Antoni Ribas, Jedd D. Wolchok, F. Stephen Hodi, Richard Kefford, Anthony M. Joshua, Wen-Jen Hwu, Tara C. Gangadhar, Amita Patnaik, Peter Hersey, Jeffrey S. Weber, Richard Wayne Joseph, Kevin Gergich, Xiaoyun (Nicole) Li, Patrick Chun, Scot Ebbinghaus, Soonmo Peter Kang, Adil Daud; The Angeles Clinic and Research Institute, Los Angeles, CA; Institut Gustave Roussy, Paris, France; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Westmead Hospital and Melanoma Institute Australia, University of Sydney, Westmead, Australia; Princess Margaret Cancer Centre, Toronto, ON, Canada; The University of Texas MD Anderson Cancer Center, Houston, TX; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; South Texas Accelerated Research Therapeutics (START) Center for Cancer Care, San Antonio, TX; University of Sydney, Sydney, Australia; Moffitt Cancer Center, Comprehensive Melanoma Research Center, Tampa, FL; Mayo Clinic Cancer Center, Jacksonville, FL; Merck & Co, Inc, North Wales, PA; Merck/MRL, Kenilworth, NJ; Merck & Co, Inc, Rahway, NJ; University of California, San Francisco, San Francisco, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


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.

2 Q3W 10 Q3W 2-sided P 2 Q3W 10 Q3W 2-sided P
ORR, %
   (95% CI)
.4835 39
Response duration,
   wk, range
7+ – 36+ 6+ – 39+ 12+ – 42+ 10+ – 39+
Median PFS,
   wk(95% CI)
24-wk PFS, % 51 48 60 50
ORR, %
   (95% CI)
.9558 27
Response duration,
   wk, range
6+ – 37+ 8+ – 37+ 12+ – 42+ 4+ – 37+
Median PFS, wk
   (95% CI)
24-wk PFS, % 45 37 57 57