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Melanoma Drug Binimetinib Submitted for FDA Consideration
A new drug application has been submitted to the FDA for binimetinib (Array BioPharma) for the treatment of patients with advanced NRAS-mutant melanoma. The submission was based on results from the pivotal phase 3 NEMO (NRAS MElanoma and MEK InhibitOr) trial, which found that binimetinib significantly extended progression-free survival (PFS), the study’s primary endpoint, compared with dacarbazine (DTIC-Dome, Bayer Pharmaceuticals).
MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown that this pathway regulates several key cellular activities, including proliferation, differentiation, survival, and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, non–small-cell lung cancer, and colorectal and thyroid cancers. Binimetinib is a late-stage small-molecule MEK inhibitor that targets key enzymes in this pathway.
In the NEMO study, binimetinib significantly extended median PFS to 2.8 months compared with 1.5 months for dacarbazine (hazard ratio [HR], 0.62; P < 0.001) in patients with advanced NRAS-mutant melanoma. In a subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab, or pembrolizumab, those who received binimetinib achieved 5.5 months of median PFS compared with 1.6 months for those receiving dacarbazine.
In addition to improving PFS, binimetinib also demonstrated significant improvement in the overall response rate (ORR) and in the disease control rate (DCR). While there was no statistically significant difference in overall survival (OS) between binimetinib and dacarbazine, median OS favored the binimetinib arm:
- The confirmed ORR was 15% in patients receiving binimetinib versus 7% in patients receiving dacarbazine.
- The DCR for patients receiving binimetinib was 58% versus 25% for those receiving dacarbazine.
- Median OS was estimated at 11.0 months in patients receiving binimetinib versus 10.1 months for those treated with dacarbazine (HR, 1.0; P = 0.499).
Binimetinib was generally well tolerated, and the adverse events reported were consistent with previous results in patients with NRAS-mutant melanoma. Grade 3 or 4 adverse events in at least 5% of patients receiving binimetinib included increased creatine phosphokinase levels and hypertension.
Source: Array BioPharma; June 30, 2016.