Array BioPharma reported over the weekend that it is withdrawing its NDA for approval of binimetinib (MEK162) monotherapy in the treatment of NRAS-mutant melanoma. The firm said discussions with and feedback from the FDA, including a late cycle review meeting on Friday, led it to conclude that clinical benefits demonstrated in the Phase III NEMO clinical trial wouldn’t be enough to support U.S. approval of the small-molecule MEK inhibitor for the NRAS-mutated melanoma indication. Array indicated that it still plans to file an NDA during 2017 for the use of binimetinib in combination with its investigational small-molecule mutant BRAF kinase inhibitor encorafenib for treating BRAF-mutated melanoma.
The FDA accepted the NDA for binemetinib monotherapy against NRAS-mutant melanoma in September 2017. Regulatory filing was based on the Phase III NEMO study (NCT01763164) comparing binimetinib therapy with dacarbazine therapy. The study met its primary progression-free survival (PFS) primary endpoint, demonstrating a median PFS of 2.8 months for binemetinib-treated patients, compared with 1.5 months for patients receiving dacarbazine. PFS in binimetinib-treated patients who received prior immunotherapy was 5.5 months, compared with 1.6 months for patients receiving dacarbazine therapy.
Array’s third late-stage clinical oncology candidate selumetinib (AZD6244, formerly ARRY-142886) is a small-molecule MEK inhibitor licensed to AstraZeneca in 2003 for global development and commercialization. The drug is undergoing pivotal studies for treating differentiated thyroid cancer and neurofibromatosis type 1, having failed in a Phase III study in lung cancer. AstraZeneca reported in August 2016 that the Phase III SELECT-1 trial evaluating selumetinib combined with docetaxel chemotherapy as second-line treatment of KRAS-mutated non-small-cell lung cancer (NSCLC) failed to meet its primary endpoint.