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Poster display session

3654 - BEACON CRC: Safety Lead-In (SLI) for the Combination of Binimetinib (BINI), Encorafenib (ENCO), and Cetuximab (CTX) in Patients (Pts) with BRAF-V600E Metastatic Colorectal Cancer (mCRC)

Date

09 Sep 2017

Session

Poster display session

Presenters

Sanne Huijberts

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

S. Huijberts1, J.H.M. Schellens1, E. Elez2, P. Cuyle3, E. Van Cutsem4, R. Yaeger5, M. Fakih6, C. Montagut7, M. Peeters8, J. Desai9, T. Yoshino10, F. Ciardiello11, H. Wasan12, A. Grothey13, K. Maharry14, A. Gollerkeri15, S. Kopetz16

Author affiliations

  • 1 Clinical Pharmacology & Medical Oncology, The Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 2 Medical Oncology, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, 08035 - Barcelona/ES
  • 3 Gastroenterology, Imelda General Hospital (Bonheiden) and University Hospitals Gasthuisberg Leuven and KU Leuven, 2820 - Leuven/BE
  • 4 Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, 3000 - Leuven/BE
  • 5 Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 6 Medical Oncology, City of Hope Comprehensive Cancer Center, 91010 - Duarte/US
  • 7 Oncology, University Hospital del Mar, 8003 - Barcelona/ES
  • 8 Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 9 Medical Oncology, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 10 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 11 Medical Oncology, Department Of Clinical And Experimental Medicine "f. Magrassi", University of Campania "Luigi Vanvitelli", 80131 - Naples/IT
  • 12 Medical Oncology, Hammersmith Hospital, Imperial College London, W12 0HS - London/GB
  • 13 Gi Medical Oncology, Mayo Clinic, 55905 - Rochester/US
  • 14 Biostatistics, Array BioPharma Inc., 80301 - Boulder/US
  • 15 Clinical Sciences, Array BioPharma Inc., 80301 - Boulder/US
  • 16 Gi Medical Oncology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
More

Resources

Abstract 3654

Background

Phase 2 data for the combination of ENCO (a selective BRAF inhibitor) + CTX (an anti-EGFR antibody) in pts with BRAFV600E mCRC showed the regimen was well tolerated and improved response rate, progression-free survival, and overall survival compared with historical controls. BEACON CRC (NCT02928224) is a randomized phase 3 study evaluating both the triplet combination BINI (a MEK inhibitor) + ENCO + CTX and the doublet combination ENCO + CTX compared with investigators’ choice of irinotecan (IRI) + CTX or FOLFIRI (folinic acid, 5-fluorouracil, and IRI) + CTX in pts with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. Here we describe the results of the SLI to determine the safety of the triplet combination.

Methods

Nine pts with BRAFV600E mCRC would receive ENCO 300 mg QD + BINI 45 mg BID + CTX 400 mg/m2 (then 250 mg/m2 QW) in 28-day cycles. If 

Results

Thirty pts received the initial dose level; median age was 59 years, 17 pts were female, and 17 had an ECOG PS of 0. DLTs were reported in 5 pts: infusion reaction following CTX (n = 2), inability to receive ≥75% dose intensity due to grade 2 retinopathy (n = 2), and grade 2 decreased ejection fraction (n = 1). The most common adverse events (% of pts with grade 1, 2, 3, 4) were diarrhea (38, 28, 3, 0), nausea (41, 3, 0, 0), dermatitis acneiform (38, 7, 0, 0), and fatigue (21, 14, 7, 0). Twenty-eight pts continue on treatment; 1 pt died due to rapid disease progression and 1 pt discontinued due to disease-related biliary obstruction. Preliminary efficacy data support the benefit of adding BINI to the doublet regimen; additional follow-up will provide mature safety and efficacy data from the SLI cohort and will be presented.

Conclusions

ENCO + BINI + CTX, at the full planned dose of each agent, was generally well tolerated. Safety and preliminary efficacy data support the initiation of the phase 3 portion of the BEACON trial.

Clinical trial identification

NCT02928224

Legal entity responsible for the study

Array BioPharma Inc.

Funding

Array BioPharma Inc.

Disclosure

E. Van Cutsem: Consulting: Bayer, Boehringer Ingelheim, Lilly, Novartis, Merck Serono. Research funding: Amgen, Bayer, Boehringer Ingelheim, Celgene, Ipsen, Merck, Novartis, Roche, Sanofi. M. Fakih: Advisory board: Array BioPharma. C. Montagut: Consulting: Merck, Amgen, Symphogen, Sanofi. J. Desai: Honoraria: Novartis, Amgen, GlaxoSmithKline. Consulting: Plexxikon, Bionomics, Roche, Novartis, Lilly. Research Funding: Novartis, Roche, GlaxoSmithKline. T. Yoshino: Research Funding: GlaxoSmithKline K.K., Boehringer Ingelheim GmbH. F. Ciardiello: Advisory Board: Roche, Merck, BMS, Lilly, Amgen, Bayer. H. Wasan: Advisory Board/Speaker Bureau: Merck Serono, Pfizer, Array BioPharma Inc. K. Maharry, A. Gollerkeri: Employment: Array BioPharma Inc. S. Kopetz: Compensation from: Amgen, Merrimack, Bayer, Array BioPharma, Genentech, MolecularMatch, Symphogen, EMD Serono, Merck. All other authors have declared no conflicts of interest.

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