LBA34 - Pembrolizumab (pembro; MK-3475) for advanced melanoma (MEL): Randomized comparison of two dosing schedules

Date 29 September 2014
Event ESMO 2014
Session Melanoma and other skin tumours
Topics Immunotherapy
Skin Cancers
Presenter Caroline Robert
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors C. Robert1, A.M. Joshua2, J.S. Weber3, A. Ribas4, F.S. Hodi5, R. Kefford6, A. Daud7, J.D. Wolchok8, W. Hwu9, T.C. Gangadhar10, A. Patnaik11, P. Hersey12, R. Dronca13, H. Zarour14, Y. Ge15, J.A. Lindia16, M. Giannotti16, S. Ebbinghaus16, S..P. Kang16, O. Hamid17
  • 1Dermatology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2Medical Oncology, Princess Margaret Cancer Centre, Toronto/CA
  • 3Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center, Tampa/US
  • 4Department Of Medicine, UCLA, Los Angeles/US
  • 5Medicine, Dana-Farber Cancer Institute, Boston/US
  • 6Crown Princess Mary Cancer Centre, Westmead Hospital and and Melanoma Institute Australia, and University of Sydney, Sydney/AU
  • 7Medicine, University of California, San Francisco/US
  • 8Immunology Program, Memorial Sloan Kettering Cancer Center, New York/US
  • 9Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 10Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US
  • 11Phase I, South Texas Accelerated Research Therapeutics, 78229 - San Antonio/US
  • 12Melanoma Biology, University of Sydney, Sydney/AU
  • 13Oncology, Mayo Clinic, Rochester/US
  • 14N/a, University of Pittsburgh, Pittsburgh/US
  • 15Bards, Merck & Co., Inc., Whitehouse Station/US
  • 16Clinical Oncology, Merck & Co., Inc., Whitehouse Station/US
  • 17Oncology Research, The Angeles Clinic and Research Institute, Los Angeles/US




Pembro has demonstrated strong antitumor activity in patients (pts) with advanced MEL at doses of 10 mg/kg every 2 weeks (Q2W), 10 mg/kg Q3W, and 2 mg/kg Q3W. Previous randomized data from KEYNOTE-001 showed no difference in efficacy or safety between 10 mg/kg Q3W and 2 mg/kg Q3W.


To formally compare the efficacy and safety of pembro dosing schedules of 10 mg/kg Q3W and 10 mg/kg Q2W, an additional 244 pts were enrolled in KEYNOTE-001 and randomized 1:1 to treatment with pembro 10 mg/kg Q3W (n = 121) or 10 mg/kg Q2W (n = 123). Ipilimumab-naive (IPI-N) pts received ≤2 prior systemic therapies; IPI-treated (IPI-T) pts were not restricted by prior therapy. Response was assessed every 12 wk. Primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review.


As of Feb 2014, median follow-up was approximately 35 wk, and all pts had ≥26 wk follow-up. Arms were balanced for known prognostic factors. Median treatment duration was 21 wk for the Q3W arm and 22 wk for the Q2W arm. Among the 224 pts evaluable for ORR (n = 108 at Q3W, 116 at Q2W), no significant difference was observed between schedules (28% at Q3W [n = 1 complete response, 29 partial responses] vs 33% at Q2W [n = 4 complete response, 34 partial responses]; P = .419). Across schedules, confirmed ORR was 33% in IPI-N (n = 115) and 28% in IPI-T (n = 109) pts. Disease control rate was 44% at Q3W and 50% at Q2W (P = .4064). 24-wk progression-free survival (PFS) rates were 43% at Q3W and 47% at Q2W, and there was no significant difference in PFS between schedules (HR, 1.19; 95% CI, 0.85–1.66; P = .298). The safety profile was similar for both schedules, with grade 3–4 treatment-related adverse events (AEs) observed in 12% of pts at Q3W and 15% at Q2W, discontinuations due to treatment-related AEs in 1% at Q3W and 3% at Q2W, and no treatment-related deaths.


Overall, pembro showed similar efficacy and safety at 10 mg/kg Q2W and 10 mg/kg Q3W in pts with advanced MEL. Considering previous randomized data showing no significant difference in efficacy and safety between pembro doses of 10 mg/kg Q3W and 2 mg/kg Q3W, the recommended pembro dose and schedule is 2 mg/kg Q3W.


C. Robert: Advisory board member for Merck, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, and Amgen; J.S. Weber: Research funding and personal fees from Merck; A. Ribas: Research funding, advisory board membership, and honoraria from Merck; F.S. Hodi: Research funding from Merck and unpaid consultant to Merck; R.F. Kefford: Travel paid by Merck, Bristol-Myers Squibb, Roche, and Novartis; advisory board membership for Merck, Bristol-Myers Squibb, GlaxoSmithKline, Roche, and Novartis; honoraria from Merck; A. Daud: Research funding from and advisory board membership for Amgen, Genentech, GlaxoSmithKline, OncoSec, and Roche; J.D. Wolchok: Research funding from Merck and Bristol-Myers Squibb and advisory board membership for Merck; W-J. Hwu: Funding for research, clinical trial support, and study drug from Merck; A. Patnaik and H. Zarour: Research funding from Merck; Y. Ge, J.A. Lindia, M. Giannotti, S. Ebbinghaus and S.P. Kang: Employee of and stock ownership in Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc;O. Hamid: Research funding from and consultant for Merck. All other authors have declared no conflicts of interest.