Binimetinib (MEK162)

Target: MEK | Indication: Melanoma

Introduction / Brief Description

Binimetinib is an oral small-molecule MEK inhibitor invented by Array. MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS.

Two Phase 3 trials with binimetinib in advanced cancer patients are currently advancing: BRAF-mutant melanoma (COLUMBUS) and NRAS-mutant melanoma (NEMO).

In December 2015, Array reported top-line results from the NEMO trial.  The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment, with a hazard ratio of 0.62, [95% CI 0.47-0.80] and a p-value of less than 0.001. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm.  In the trial, binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS melanoma patients. 

Array plans to submit binimetinib to regulatory authorities for marketing approval in NRAS-mutant melanoma during the first half of 2016.  Results from the NEMO trial including progression free survival, overall survival, objective response rate, safety and prespecified subgroup analyses including outcomes in patients who received prior treatment with immunotherapy will be presented at a medical conference in 2016.  

In addition, Array expects top-line results from Part 1 of the COLUMBUS trial in the first half of 2016 and projects a regulatory filing of binimetinib and encorafenib in 2016.  The MILO Phase 3 study in patients with low-grade serous ovarian cancer continues to enroll patients, and Array estimates enrollment to be complete in 2016 with the availability of top-line data, along with a projected regulatory filing, in 2017.

In addition to these registration trials, early-stage studies have been initiated to evaluate binimetinib in numerous solid tumors and hematologic malignancies.

BRAF-mutant Melanoma and NRAS-mutant Melanoma

Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with 76,380 new cases and over 10,130 deaths from the disease projected in 2016. Novel therapies that target the RAS/RAF/MEK/ERK pathway have a strong scientific rationale for activity in this disease, as melanoma is often characterized by activating mutations in BRAF (approximately 50% of patients) and NRAS (approximately 20% of patients). There are presently no approved therapies specifically targeting NRAS-mutant melanoma.

 

Clinical Trials

Trial Data
Trial Title
Program: Binimetinib (MEK162)
Phase: 3
Status: Active, not recruiting
Disease: NRAS mutant melanoma
Sponsor: Novartis
Trial Information: NCT01763164
Trial Title: Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma (NEMO)
Program: Binimetinib (MEK162)
Phase: 3
Status: Recruiting
Disease: BRAF V600 mutant melanoma
Sponsor: Novartis
Trial Information: NCT01909453
Trial Title: Study Comparing Combination of LGX818 Plus MEK162 and LGX818 Monotherapy Versus Vemurafenib in BRAF Mutant Melanoma (COLUMBUS)
Program: Binimetinib (MEK162)
Trial Information: ClinicalTrials.gov
Trial Title: Other clinical Trials

Publications

Binimetinib / Cancer

01/21/2016

American Society of Clinical Oncology GI 2016

A Phase I Study of MEK162 and FOLFOX in chemotherapy-resistant metastatic colorectal cancer

M. Cho, et al.

Binimetinib / Cancer

09/28/2015

European Cancer Congress

A Phase 1b/2 Study of Ribociclib (LEE011; CDK4/6 inhibitor) in Combination With Binimetinib (MEK162; MEK inhibitor) in Patients With NRAS‐Mutant Melanoma

C. van Herpen, M.D., Ph.D, et al.

Binimetinib / Cancer

09/27/2015

European Cancer Congress

R. Dummer, M.D., et al.

Binimetinib / Cancer

05/31/2015

American Society of Clinical Oncology Meeting

SUCCESSFUL IMPLEMENTATION OF A NOVEL TRIAL MODEL – THE SIGNATURE PROGRAM

J. Peguero, et al.

Binimetinib / Cancer

05/30/2015

American Society of Clinical Oncology Meeting

A phase Ib/II study of MEK162 (binimetinib) in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST)

P.Chi, et al.

 


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