The FDA has accepted a new drug application (NDA) for binimetinib (Array BioPharma), with a target action date under the Prescription Drug User Fee Act of June 30, 2017. The NDA submission was completed in late June 2016, based on findings from the pivotal phase 3 NEMO (NRAS Melanoma and MEK Inhibitor) trial in patients with NRAS-mutant melanoma.
The FDA indicated that it plans to hold a meeting of its Oncologic Drugs Advisory Committee (ODAC) as part of the review process.
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 occurs in many cancers, such as melanoma and colorectal or thyroid cancers. Binimetinib is a late-stage small-molecule MEK inhibitor that targets key enzymes in this pathway.
The NEMO trial is an international, randomized study evaluating the safety and efficacy of binimetinib (45 mg twice daily) compared with that of dacarbazine (1,000 mg/m2 dosed every three weeks). Prior immunotherapy treatment was allowed, and patients underwent radiographic assessment of their disease status every six weeks. More than 100 sites in North America, Europe, South America, Asia, and Australia participated in the study.
The trial met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine. The median PFS in the binimetinib arm was 2.8 months compared with 1.5 months in the dacarbazine arm. In the prespecified subset of patients who received immunotherapy, including ipilimumab, nivolumab, and pembrolizumab, those who were treated with binimetinib experienced 5.5 months of median PFS compared with 1.6 months for those treated with dacarbazine.
Array BioPharma anticipates that the primary consideration for marketing approval will be the results for the primary endpoint of this trial. In addition to improving PFS, binimetinib also demonstrated improvement in the overall response rate and the disease control rate. While there was no statistically significant difference in overall survival (OS) between the two treatment arms, median OS favored the binimetinib arm.
Binimetinib is currently being studied in several other oncology trials, including the phase 3 COLUMBUS study, which is evaluating encorafenib in combination with binimetinib in patients with BRAF-mutant melanoma, and the recently initiated BEACON trial, which is looking at encorafenib in combination with binimetinib and cetuximab in patients with BRAF V600E-mutant colorectal cancer. Array BioPharma expects results from the COLUMBUS study to be available during the third quarter of 2016.
Binimetinib is an investigational medication and is not currently approved for use in any country.
Source: Array BioPharma; September 1, 2016.