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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

Date

09 Sep 2017

Session

Melanoma and other skin tumours

Topics

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

Presenters

Antoni Ribas

Citation

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

Authors

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

Background

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.

Methods

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.

Results

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.

Conclusions

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

Funding

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

Disclosure

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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