Date: 2016-06-06
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Array BioPharma (USA - CO)
Product: binimetinib (MEK162)
Action
mechanism: kinase inhibitor. MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals cancer cell proliferation and survival. MEK has been shown to be activated in several tumor types such as non-small cell lung cancer, melanoma, thyroid cancer, ovarian cancer, and, in particular, tumors with BRAF and NRAS mutations. Binimetinib (MEK162) is a small molecule MEK inhibitor that targets a key position in this pathway. This small molecule selective inhibitor of the kinases MEK1 and MEK2 has been licensed to Novartis in 2010.
Disease: advanced NRAS mutant melanoma
Therapeutic area: Cancer - Oncology - Rare diseases
Country: Argentina,Australia,Austria,Belgium,Brazil,Canada,Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Republic of Korea, The Netherlands, Poland, Portugal, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey,UK, USA
Trial
details: The NEMO trial is an international, randomized Phase 3 study in patients with advanced NRAS-mutant melanoma. 402 patients were randomized 2:1 to receive continuous 45 mg BID binimetinib or 1,000 mg/m2 dacarbazine dosed every three weeks. Prior immunotherapy treatment was allowed. The primary endpoint of the study is progression-free survival, and overall survival is a key secondary endpoint. Patients underwent radiographic assessment of disease status every six weeks, and assessment of progression was determined by blinded central review. Over 100 sites across North America, Europe, South America, Asia and Australia participated in the study. (NCT01763164)
Latest
news: * On June 6, 2016, Array BioPharma announced full results at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract No. 9500) from the pivotal Phase 3 NEMO (NRAS MELANOMA AND MEK INHBITOR) trial of binimetinib. The study found binimetinib significantly extended median progression-free survival (PFS), the study's primary endpoint, at 2.8 months, as compared with 1.5 months observed with dacarbazine [hazard ratio (HR)=0.62 (95% CI 0.47-0.80), p<0.001] – the first trial to ever meet a PFS endpoint in patients with advanced NRAS-mutant melanoma. In the pre-specified subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab or pembrolizumab, patients who received binimetinib experienced 5.5 months of median PFS (95% CI, 2.8–7.6), compared with 1.6 months for those receiving treatment with dacarbazine (95% CI, 1.5–2.8). In addition to improving PFS, binimetinib also demonstrated significant improvement in overall response rate (ORR) and disease control rate (DCR). While there was no statistically significant difference demonstrated in overall survival, the median overall survival (mOS) favored the binimetinib arm. Confirmed ORR was 15 percent (95% CI, 11-20 percent) in patients receiving binimetinib vs. 7 percent (95% CI, 3-13 percent) in patients receiving dacarbazine. DCR for patients receiving binimetinib was 58 percent (95% CI, 52-64 percent) vs. 25 percent (95% CI, 18-33 percent) for patients receiving dacarbazine. mOS was estimated at 11.0 months in patients receiving binimetinib vs. 10.1 months for patients treated with dacarbazine [(HR) = 1.0 (95% CI 0.75-1.33), p=0.499].Binimetinib was generally well-tolerated and the adverse events (AEs) reported were consistent with previous results in NRAS-mutant melanoma patients. Grade 3/4 AEs reported in greater than or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase (CPK) and hypertension. Based on data on the NEMO trial Array BioPharma plans to submit a regulatory filing for binimetinib in NRAS-mutant melanoma later in June. * On September 29, 2014, final results from a Phase 2 trial of binimetinib in patients with advanced NRAS mutant melanoma were presented at the European Society for Medical Oncology (ESMO) Annual Meeting in Madrid, Spain. Results from the 117 patient Phase 2 study showed median progression free survival (mPFS) of 3.6 months and objective response rate (ORR) of 14.5%, including one patient who achieved a complete response. These findings were consistent with previously disclosed interim results at the American Society of Clinical Oncology 2012 annual meeting. In addition, the median overall survival (mOS) of 12.2 months is encouraging for this patient population, which has a particularly poor prognosis. Adverse events in the Phase 2 study were generally mild to moderate. The most frequently observed adverse events included acneiform dermatitis, increased blood creatine phosphokinase and peripheral edema, which are consistent with previous results reported for the MEK inhibitor class.
