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Melanoma and other skin tumours

4143 - Results of COLUMBUS Part 2: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) Versus ENCO in BRAF-Mutant Melanoma

Date

09 Sep 2017

Session

Melanoma and other skin tumours

Topics

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

Presenters

Reinhard Dummer

Citation

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

Authors

R. Dummer1, P.A. Ascierto2, H. Gogas3, A.M. Arance4, M. Mandala5, G. Liszkay6, C. Garbe7, D. Schadendorf8, I. Krajsová9, R. Gutzmer10, V. Chiarion Sileni11, C. Dutriaux12, J.W.B. de Groot13, N. Yamazaki14, C. Loquai15, L.A. de Parseval16, M. Pickard17, V. Sandor18, C. Robert19, K.T. Flaherty20

Author affiliations

  • 1 Department Of Dermatology, University Hospital Zürich-Dermatology, 8091 - Zürich/CH
  • 2 Unit Of Melanoma, Cancer Immunotherapy And Innovative Therapy, Istituto Nazionale Tumori Fondazione Pascale, Naples/IT
  • 3 Department Of Internal Medicine, National and Kapodestrian University of Athens, Laikon Hospital, Athens/GR
  • 4 Department Of Medical Oncology, Hospital Clinic of Barcelona, Barcelona/ES
  • 5 Department Of Oncology And Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo/IT
  • 6 Department Of Dermatology, National Institute of Oncology, Budapest/HU
  • 7 Department Of Dermatology, Division Of Dermatooncology, Eberhard Karls University, Tuebingen/DE
  • 8 Department Of Dermatology, University Hospital Essen, Heidelberg/DE
  • 9 Department Of Dermato-oncology, University Hospital Prague and Charles University First Medical Faculty, Prague/CZ
  • 10 Department Of Dermatology And Allergy, Skin Cancer Center, Hannover Medical School, Hannover/DE
  • 11 Melanoma Cancer Unit, Oncology Institute of Veneto IRCCS, Padua/IT
  • 12 Department Of Oncologic Dermatology, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux/FR
  • 13 Department Of Medical Oncology, Isala, Zwolle/NL
  • 14 Department Of Dermatologic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 15 Department Of Dermatology, University Medical Center, Mainz/DE
  • 16 Translational Clinical Oncology, Novartis Pharma AG, Basel/CH
  • 17 Biostatistics And Data Management, Array BioPharma Inc., Boulder/US
  • 18 Medical Affairs, Array BioPharma, Boulder/US
  • 19 Department Of Medicine, Institut Gustave Roussy, Villejuif/FR
  • 20 Department Of Medical Oncology, Massachusetts General Hospital, 2114 - Boston/US
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Abstract 4143

Background

The addition of a MEK inhibitor (MEKi) to a BRAF inhibitor (BRAFi) in BRAF V600-mutant metastatic melanoma improves efficacy, including progression-free survival (PFS) and objective response rate (ORR), and attenuates some BRAFi−associated toxicities. Part 1 of the COLUMBUS study met its primary endpoint. The BRAFi ENCO 450 mg once daily (QD) + the MEKi BINI 45 mg twice daily (BID; COMBO450) improved PFS vs vemurafenib (VEM) alone and ENCO 300 mg QD (ENCO300) alone in patients (pts) with advanced BRAF V600-mutant melanoma. The tolerability of COMBO450 was favorable compared with VEM or ENCO300. In Part 2, the contribution of BINI to the combination was further evaluated by maintaining the same dose of ENCO in the combination (ENCO 300 mg QD + BINI 45 mg BID; COMBO300) and comparator arms (ENCO300 alone; ClinicalTrials.gov, NCT01909453; EudraCT, 2013-001176-38).

Methods

Pts were randomized 3:1 to COMBO300 or ENCO300. Data from ENCO300 arms in Parts 1 + 2 were combined for the primary efficacy comparison of PFS by independent blinded central review (BCR). Other analyses included PFS for COMBO300 vs ENCO300 (Part 2 only), ORR, complete response (CR) and partial response (PR) by BCR and local review, and safety.

Results

Pt characteristics are presented in the Table. Median PFS (95% CI) for COMBO300 was 12.9 mo (10.1–14.0) vs 9.2 mo (7.4–11.0) for ENCO300 (Parts 1 + 2) and 7.4 mo (5.6–9.2) for ENCO300 (Part 2). The hazard ratio (HR) for COMBO300 was 0.77 (0.61–0.97; P = 0.029, 2-sided) vs ENCO300 (Parts 1 + 2) and 0.57 (0.41–0.78; P

Conclusions

COMBO300 meaningfully improved PFS, ORR, and tolerability vs ENCO300, confirming the contribution of BINI to both efficacy and safety.

Clinical trial identification

Trial protocol number, CMEK162B2301 (release date, July 13, 2015)

Legal entity responsible for the study

Array BioPharma Inc

Funding

Array BioPharma Inc and Novartis Pharmaceuticals Corporation

Disclosure

R. Dummer: Honoraria from and consulting/advisory role for Roche, Bristol-Myers Squibb, GSK, MSD, Novartis, and Amgen; research funding from Roche, Bristol-Myers Squibb, GSK, MSD, and Novartis. P.A. Ascierto: Consulting fees from Bristol-Myers Squibb, Roche/Genentech, MSD, Ventana, Novartis, Amgen, and Array BioPharma; research funding from Bristol-Myers Squib, Roche/Genentech, Ventana, and Array BioPharma H. Gogas: Consultant for Roche, Bristol-Myers Squibb, MSD, Novartis, and Amgen. A. Arance: Honoraria from and consulting/advisory role and speakers bureau for Novartis, Roche, MSD, and Bristol-Myers Squibb; travel expenses from Roche and Bristol-Myers Squibb. M. Mandala: Honoraria from Novartis, GSK, Bristol-Myers Squibb, MSD, and Roche; speakers bureau for Novartis, GSK, Roche, and Bristol-Myers Squibb; advisory board member for Novartis, Amgen, MSD, and Bristol-Myers Squibb; research funding from Roche. C. Garbe: Honoraria and travel expenses from and served in a consulting/advisory role and speakers bureau member for Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Philogen; research funding for University Hospital Tübingen from Bristol-Myers Squibb, Novartis, and Roche. D. Schadendorf: Honoraria and travel expenses from and consulting/advisory role and speakers bureau for Amgen, Bristol-Myers Squibb, Novartis, Roche, and MSD; research funding for University Hospital Essen from Amgen, Bristol-Myers Squibb, Novartis, Roche, and MSD. I. Krajsová: Advisory board member for Bristol-Myers Squibb, Novartis, Roche, MSD; travel expenses from Bristol-Myers Squibb and MSD. R. Gutzmer: Consulting fees and/or honoraria from Roche, Bristol-Myers Squibb, MSD, GSK, Novartis, Almirall, LEO, Amgen, Pfizer, Merck Serono, Boehringer Ingelheim; research funding from Roche, Novartis, Pfizer, Pierre Fabre, Johnson & Johnson; travel expenses from Bristol-Myers Squibb, Roche. V. Chiarion Sileni: Honoraria received from Novartis, GSK, Bristol-Myers Squib, MSD, and Roche; speakers bureau for Novartis, GSK, Roche, and Bristol-Myers Squibb; advisory board member for Novartis, Amgen, MSD, Bristol-Myers Squibb, and Roche. J.W.B. de Groot: Consulting/advisory role for Amgen, Bayer, Celgene, Roche, Bristol-Myers Squibb, GSK, MSD, and Merck Serono. N. Yamazaki: Advisory role for Chugai Pharma, Bristol-Myers Squibb Japan, and Ono Pharmaceutical; honoraria from Chugai Pharma, Bristol-Myers Squibb Japan, Ono Pharmaceutical, GlaxoSmithKline, Takeda, AstraZeneca Japan, Boehringer Ingelheim, and Maruho. C. Loquai: Advisory board member for Roche, Novartis, Bristol-Myers Squibb, MSD, BioNTech, Pierre Fabre, and Amgen; speakers fees from Roche, Novartis, B Bristol-Myers Squibb MS, and MSD; travel expenses from Roche, Novartis, Bristol-Myers Squibb, MSD, and Amgen. L.A. de Parseval: Employee of Novartis Pharma AG; may own stock or stock options. M. Pickard: Employee of Array BioPharma; may own stock or stock options. V. Sandor: Employee/leadership role at Array BioPharma; stock or other ownership of Array BioPharma and Incyte Corp. C. Robert: Consultant for Roche, Novartis, Bristol-Myers Squibb, MSD, and Amgen. K.T. Flaherty: Honoraria from and consulting/advisory role for Novartis and Array BioPharma; research funding from Novartis. All other authors have declared no conflicts of interest.

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