Merck Partners with Array BioPharma and Pierre Fabre to Initiate BRAF-mutant CRC Phase III Trial - Seite 2

"We are pleased to join Merck on this innovative trial for patients with BRAF-mutant metastatic colorectal cancer," said Victor Sandor, MD, Chief Medical Officer of Array BioPharma. "The encouraging results from our Phase II study suggest that concurrent inhibition of EGFR and enzymes in the MAPK signaling pathway has the potential to improve outcomes for this patient population, and we look forward to the results of this further investigation."

Approximately 650 patients are expected to be enrolled by 2018 and, after a lead-in period to assess the safety and tolerability of Erbitux plus encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor), will be randomized to receive one of the two novel combinations, or investigator's choice. The primary endpoint of the trial is overall survival. Key secondary endpoints include progression-free survival, objective response rate, duration of response, safety and tolerability. The trial will also assess health-related quality of life.

References 

1. Barras D. Biomark Cancer. 2015;7(Suppl 1):9-12.
2. Saridaki Z. PLoS One. 2013 Dec 18;8(12):e84604. doi: 10.1371.
3. Vaughn CP et al. Genes Chromosomes Cancer 2011;50(5):307−12.
4. Bokemeyer C et al. J Clin Oncol 2014;32:(Suppl 4): abstr 3505.
5. Van Cutsem E et al. J Clin Oncol 2015;33(7):692-700.
6. Stintzing S et al. Ann Oncol 2014;25(Suppl 4) abstr LBA11.
7. Lenz H et al. Ann Oncol 2014;25(Suppl 4) abstr 501O.
8. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr , accessed June 2015.

About BRAF Mutations 

BRAF is an important actor in the epidermal growth factor receptor(EGFR)-mediated mitogen-activated protein kinase (MAPK) pathway, which strongly impacts cell growth and proliferation, as well as cell migration, cell death and cell survival.^[1]

About mCRC 

Approximately half of patients with mCRC have RAS wild-type tumors and half have RAS mutant tumors.^[3] Results from studies assessing RAS mutation status in patients with mCRC have shown that anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies, such as Erbitux^® (cetuximab), can improve outcomes in patients with RAS wild-type mCRC.^[4]-[7] CRC is the third most common cancer worldwide, with an estimated incidence of more than 1.36 million new cases annually.^[7] An estimated 694,000 deaths from CRC occur worldwide every year, accounting for 8.5% of all cancer deaths and making it the fourth most common cause of death from cancer.^[8] Almost 55% of CRC cases are diagnosed in developed regions of the world, and incidence and mortality rates are substantially higher in men than in women.^[8]