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Melanoma and other skin tumours

2503 - KEYNOTE-022 update: phase 1 study of first-line pembrolizumab (pembro) plus dabrafenib (D) and trametinib (T) for BRAF-mutant advanced melanoma


09 Sep 2017


Melanoma and other skin tumours


Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA);  Immunotherapy;  Melanoma


Antoni Ribas


Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377


A. Ribas1, F..S. Hodi2, D. Lawrence3, V. Atkinson4, S. Agarwal5, M.S. Carlino6, R. Fisher7, G.V. Long8, W.H. Miller9, Y. Huang10, B. Homet Moreno11, N. Ibrahim11, O. Hamid12

Author affiliations

  • 1 School Of Medicine, University of California, Los Angeles, 90024 - Los Angeles/US
  • 2 Medical Oncology, Dana–Farber Cancer Institute, Boston/US
  • 3 Oncology, Massachusetts General Hospital, Boston/US
  • 4 Oncology, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane/AU
  • 5 Oncology, Indiana University Health Goshen Center for Cancer Care, Goshen/US
  • 6 Medical Oncology, Westmead and Blacktown Hospitals, The University of Sydney, and Melanoma Institute Australia, Sydney/AU
  • 7 Oncology, Auckland District Health Board, Auckland/NZ
  • 8 Oncology, Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney/AU
  • 9 Oncology, Segal Cancer Centre, Jewish General Hospital and McGill University, Montreal/CA
  • 10 Oncology, Novartis, East Hanover/US
  • 11 Oncology, Merck & Co., Inc., Kenilworth/US
  • 12 Research, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US


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Abstract 2503


Combination of anti–PD-1 agents with BRAF/MEK inhibitors (i) may provide synergistic antitumor effects in BRAF-mutant melanoma. The ph 1/2 KEYNOTE-022 study (NCT02130466) is assessing safety and antitumor activity of recommended doses of pembro + BRAFi D + MEKi T; updated and additional ph 1 results are reported.


Treatment-naive pts with BRAFV600E/K-mutant stage III/IV melanoma received pembro 2 mg/kg Q3W + D 150 mg BID + T 2 mg QD. Primary end point was safety; AEs were graded per CTCAE v4.0. Efficacy end points were ORR, PFS, and OS. Data cutoff: Mar 1, 2017.


Of the 15 pts enrolled, 10 (66.7%) had PD-L1+ tumors (≥1% staining), 13 (86.7%)/2 (13.3%) had ECOG PS 0/1, and 1 (6.7%) had stable brain metastases. Median follow-up was 19.7 mo (range, 15.9-31.1). 3/15 (20.0%) pts had DLTs (pt 1 had gr 4 neutropenia; pt 2 had gr 4 ALT increase; and pt 3 had gr 4 ALT, gr 3 AST, and gr 3 GGT increase); all resolved. Thus, this dose was the MTD and recommended ph 2 regimen. 11 (73%) pts had gr 3-4 TRAEs; ALT increase, AST increase, and pyrexia occurred in ≥ 20% of pts. 7 (46.7%) pts had immune-mediated AEs, most commonly hyperthyroidism in 3 pts (2 gr 1 and 1 gr 2) and hypothyroidism in 4 pts (all gr 1). Treatment was discontinued (d/c) for 2 events (1 gr 2 pneumonitis and 1 gr 3 autoimmune hepatitis) and was interrupted for 3 events (1 gr 1 hyperthyroidism, 1 gr 2 anterior uveitis, and 1 gr 3 erythematous rash); all resolved. ORR (RECIST v.1.1, investigator; confirmed + unconfirmed) was 67%; 1 pt had CR, 9 had PR; an additional 2 pts had SD and 3 had PD. ORR (RECIST v.1.1, investigator; confirmed only) was 53%; 8 pts had PR; an additional 3 pts had SD and 4 had PD. Median time to response was 2.8 mo (range, 2.2-3.0); median DOR was not reached (range, 2.8-26.5 mo). Among the 8 pts with confirmed ORR, 6 had ongoing responses and 2 had progression at data cutoff. 2 pts remained on triplet therapy, 2 d/c D + T, and 4 d/c pembro + D + T as of last follow-up.


Updated results show that approved doses of pembro + D + T continue to demonstrate promising antitumor activity for BRAF-mutant melanoma. A randomized ph 2 study is currently evaluating this triplet regimen as first-line therapy for BRAF-mutant melanoma.

Clinical trial identification

NCT02130466, May 1, 2014

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA


Merck & Co., Inc., Kenilworth, NJ, USA


A. Ribas: Stock ownership with Kite Pharma; honoraria with Amgen, Pfizer, Roche, and Merck F.S. Hodi: Advisory board member with Merck, Genentech, Novartis, EMD Serono, and Amgen; research funding from Bristol-Myers Squibb. V. Atkinson: Advisory board member with MSD, Novartis, and Pierre Fabre; speakers\' bureau involvement with MSD, Bristol-Myers Squibb, and Novartis; honoraria with MSD, Bristol-Myers Squibb, and Novartis; travel expenses from MSD, Bristol-Myers Squibb, and Novartis. M.S. Carlino: Advisory board member with Bristol-Myers Squibb, Merck, Amgen, and Novartis; honoraria from Merck and Bristol-Myers Squibb. G.V. Long: Advisory board member with Amgen, Bristol-Myers Squibb, Array, Merck MSD, Novartis, Pierre-Fabre, and Roche; honoraria from Bristol-Myers Squibb, Roche, and Merck MSD. W.H. Miller: Consultant fees from Bristol-Myers Squibb, Roche, Novartis, Merck, GSK, and Amgen. Y. Huang: Employment with Novartis. B. Homet Moreno: Employment with Merck; stock ownership with Merck. N. Ibrahim: Employment with Merck; stock ownership with Merck and GSK. O. Hamid: Advisory board member Amgen, Novartis, Roche, Bristol-Myers Squib, Merck; speakers\' bureau Bristol-Myers Squibb, Genentech, Novartis, Amgen; research funding AstraZeneca, Bristol-Myers Squibb, Celldex, Genentech, Immunocore, Incyte, Merck, Merck Serono, MedImmune, Novartis, Pfizer, Rinat, Roche. All other authors have declared no conflicts of interest.

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