133842-144

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

Subcategory: 
Category: 
Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
LBA9000^
Citation: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA9000^)
Author(s): 
Antoni Ribas, F. Stephen Hodi, Richard Kefford, Omid Hamid, Adil Daud, Jedd D. Wolchok, Wen-Jen Hwu, Tara C. Gangadhar, Amita Patnaik, Anthony M. Joshua, Peter Hersey, Jeffrey S. Weber, Roxana Stefania Dronca, Hassane M. Zarour, Kevin Gergich, Xiaoyun (Nicole) Li, Robert Iannone, Soonmo Peter Kang, Scot Ebbinghaus, Caroline Robert; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; Dana-Farber Cancer Institute, Boston, MA; Westmead Hospital and Melanoma Institute Australia, University of Sydney, Westmead, Australia; The Angeles Clinic and Research Institute, Los Angeles, CA; University of California, San Francisco, San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY; 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; Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Sydney, Sydney, Australia; Moffitt Cancer Center, Comprehensive Melanoma Research Center, Tampa, FL; Mayo Clinic, Department of Medical Oncology, Rochester, MN; University of Pittsburgh Cancer Institute, Pittsburgh, PA; Merck & Co, Inc, North Wales, PA; Merck, North Wales, PA; Merck & Co, Inc, Rahway, NJ; Institut Gustave Roussy, Paris, France

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

Abstract Disclosures

Abstract: 

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

Presentations by Antoni Ribas:

  1. Meeting: 2010 ASCO Annual Meeting
    Session: Melanoma/Skin Cancers (Oral Abstract Session)
    Discussant: Antoni Ribas