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Poster display session

4915 - A randomized, double-blind, placebo-controlled, phase III study comparing the combination of PDR001, dabrafenib and trametinib versus placebo, dabrafenib and trametinib in previously untreated patients with unresectable or metastatic BRAF V600–mutant melanoma (COMBI-i)

Date

10 Sep 2017

Session

Poster display session

Presenters

Eduard Gasal

Citation

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

Authors

E. Gasal1, A.M. Arance Fernandez2, P.A. Ascierto3, V. Atkinson4, R. Dummer5, K.T. Flaherty6, J. Grob7, J. Hansson8, J. Hassel9, J. Larkin10, C. Lebbé11, G.V. Long12, P. Lorigan13, W. Miller14, P. Nathan15, A. Ribas16, C. Robert17, D. Schadendorf18, H. Tawbi19, A. Upalawanna20

Author affiliations

  • 1 Medical Oncology, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 2 Department Of Medical Oncology, Hospital Clínic Barcelona, 8036 - Barcelona/ES
  • 3 Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Napoli/IT
  • 4 Department Of Medical Oncology, University of Queensland, 4072 - Brisbane/AU
  • 5 Department Of Dermatology, University of Zurich Hospital, 8091 - Zürich/CH
  • 6 Medicine, Dana-Farber Cancer Institute/Harvard Medical School and Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 7 Dermatology, Aix-Marseille University and APHM Hospital CHU Timone, Marseille/FR
  • 8 Department Of Oncology-pathology, Karolinska Institute, Stockholm/SE
  • 9 Department Of Dermatology And Nct, Universität Heidelberg, 69120 - Heidelberg/DE
  • 10 Medicine, Royal Marsden Hospital, London/GB
  • 11 Aphp Dermatology And Cic Departments, Hôpital Saint-Louis University Paris Diderot, Paris/FR
  • 12 Melanoma Medical Oncology, Melanoma Institute Australia, University of Sydney, and Mater Hospital, Sydney/AU
  • 13 Division Of Molecular & Clinical Cancer Sciences, The Christie NHS Foundation Trust, Manchester/GB
  • 14 Departments Of Oncology And Medicine, McGill University, Montreal/CA
  • 15 Department Of Medical Oncology, Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 16 Department Of Medicine, UCLA Medical Center, 90095-1781 - Los Angeles/US
  • 17 Department Of Medicine, Gustave Roussy Comprehensive Cancer Center, 94800 - Villejuif–Paris Sud/FR
  • 18 Department Of Dermatology, University Hospital Essen and German Cancer Consortium, 45417 - Essen/DE
  • 19 Department Of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 20 Medical Oncology, Novartis Pharma AG, 4002 - Basel/CH
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Resources

Abstract 4915

Background

Checkpoint inhibitor and targeted therapies are both important tools in the management of BRAF V600–mutated unresectable or metastatic melanoma. Although these therapies have improved responses and overall survival, many patients still progress and die from this disease. Thus, additional treatment strategies are needed to improve durability of responses and related long-term outcomes in these patients. Based on preclinical and preliminary clinical data, BRAF and MEK inhibitors can reverse the oncogenic BRAF-induced immune-suppressive phenotype through enhanced melanoma antigen expression and enhanced tumor antigen-specific T-lymphocyte recognition in vivo. These data suggest that there is potential clinical benefit in combining dabrafenib and trametinib with checkpoint inhibitor therapy.

Trial design

The 3-part COMBI-i phase 3 study (NCT02967692) will evaluate the safety and efficacy of PDR001, an investigational anti–programmed death 1 antibody, in combination with dabrafenib and trametinib in previously untreated patients with BRAF V600–mutated unresectable or metastatic melanoma. In part 1, a safety run-in will establish the recommended phase 3 regimen (RP3R) for use in part 3 using an adaptive Bayesian logistic regression model. In part 2, tissue and blood samples from the biomarker cohort will be used to characterize baseline immune markers and explore potential immune marker modulation by the triplet therapy. Part 3 is the randomized, double-blind, placebo-controlled portion that will open once the RP3R has been determined. Approximately 500 patients will be randomized 1:1 to receive either PDR001 in combination with dabrafenib and trametinib or placebo in combination with dabrafenib and trametinib, with randomization stratified based on Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level. The primary endpoint will be progression-free survival per investigator’s assessment according to RECIST v1.1. Overall survival will be a key secondary endpoint.

Clinical trial identification

NCT02967692 First received: November 16, 2016

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

E. Gasal: Employment: Novartis Stock or Other Ownership: Amgen Inc, Novartis. A.M. Arance Fernandez: Honoraria, Consulting/Advisory Role, and Speakers Bureau: Roche, Bristol-Myers Squibb, MSD, and Novartis Travel/Accommodations/Expenses: Roche, Bristol-Myers Squibb P.A. Ascierto: Consulting/Advisory Role: Bristol-Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Amgen, Array BioParma, Merck Serono Research Funding: Bristol-Myers Squibb, Roche/Genentech, Array BioPharma. V. Atkinson: Honoraria and Speakers Bureau: Bristol-Myers Squibb, MSD, Novartis, Roche Consulting/Advisory Role: Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD, Novartis. R. Dummer: Honoraria and Consulting/Advisory Role: Roche, Bristol-Myers Squibb, MSD, Novartis, GlaxoSmithKline, Amgen, Takeda, Pierre Fabre Research Funding: Roche, GlaxoSmithKline, Bristol-Myers Squibb, Novartis, MSD, Takeda, Pierre Fabre. K.T. Flaherty: Consulting/Advisory Role: Novartis. J-J. Grob: Honoraria and Consulting/Advisory Role: Bristol-Myers Squibb, Roche, MSD, Novartis Speakers Bureau: Novartis Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD, Roche, Novartis. J. Hansson: Consulting/Advisory Role: Roche, Novartis, Merck, Bristol-Myers Squibb Travel/Accommodations/Expenses: Novartis. J. Hassel: Honoraria: Bristol-Myers Squibb, MSD, Roche, GlaxoSmithKline, Novartis, Amgen Research Funding: Bristol-Myers Squibb Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD, Amgen, GlaxoSmithKline. J. Larkin: Honoraria: Bristol-Myers Squibb, MSD, Pfizer, Novartis, Eisai, GlaxoSmithKline, Roche Research Funding: Bristol-Myers Squibb, MSD, Pfizer, Novartis. C. Lebbé: Honoraria, Consulting/Advisory Role: Roche, Bristol-Myers Squib, Novartis, Amgen, MSD Speakers Bureau: Bristol-Myers Squib, Amgen, Roche, Novartis Research Funding: Roche, Bristol-Myers Squib Travel/Accommodations/Expenses: Roche, Bristol-Myers Squib, Amgen. G.V. Long: Consulting/Advisory Role: Bristol-Myers Squibb, Merck, Novartis, Amgen, Roche P. Lorigan: Consulting/Advisory Role: Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Amgen, GlaxoSmithKline Speakers Bureau: Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Roche Travel/Accommodations/Expenses: Merck Sharp & Dohme, Bristol-Myers Squibb. W. Miller: Honoraria: Bristol-Myers Squib, Merck, Roche, Novartis, GlaxoSmithKline Consulting/Advisory Role: Bristol-Myers Squib, Merck, Roche, Novartis, Amgen, GlaxoSmithKline Research Funding: Bristol-Myers Squib, Novartis, GlaxoSmithKline, Roche, AstraZeneca, Merck, MethylGene, Bayer, Amgen, MedImmune. P. Nathan: Consulting/Advisory Role: AztraZeneca, Bristol-Myers Squibb, MSD, Immunocore, Pfizer, Pierre Fabre, Novartis, GlaxoSmithKline, Ispen Speakers Bureau: Bristol-Myers Squibb, Novartis Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD. A. Ribas: Consulting/Advisory Role: Merck, Amgen, Genentech/Roche, Novartis, Lilly Stock or Other Ownership: Kite Pharma, Compugen, FLX Bio, CytomX Therapeutics, Arcus Ventures. C. Robert: Honoraria and Consulting/Advisory Role: Bristol-Myers Squibb, Roche, Merck, Novartis, Amgen, GlaxoSmithKline. D. Schadendorf: Honoraria, Speakers Bureau and Travel/Accommodations/Expenses: Amgen, Bristol-Myers Squibb, Novartis, MSD, Roche Consulting/Advisory Role: Bristol-Myers Squibb, Novartis, MSD, Roche, Array Research Funding: Bristol-Myers Squibb, Novartis. H. Tawbi: Consulting/Advisory Role: Novartis Research Funding: Bristol-Myers Squibb, Novartis, Merck. A. Upalawanna: Employment and Stock or Other Ownership: Novartis.

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