NDAs Filed for Two Melanoma Drugs

GlaxoSmithKline (GSK) is seeking the FDA’s approval for single-agent use of dabrafenib and trametinib, two targeted therapies for the treatment of patients with metastatic melanoma who harbor BRAF V600 gene mutations.

The company announced that it has filed separate New Drug Applications (NDAs) indicated for patients with unresectable or metastatic melanoma with BRAF V600 mutations detected by an FDA-approved test.

GSK has partnered with bioMérieux SA, a diagnostic company headquartered in France, on the development of an assay to detect BRAF V600 mutations, including V600E and V600K, as part of its plan to study the two drugs. The test is being used in an ongoing phase III trial of a combination treatment with both drugs.

Both drugs target the mitogen-activated protein kinase (MAPK) pathway, which includes the BRAF and MEK genes. Dabrafenib inhibits BRAF while trametinib blocks MEK activity.

Research into the two drugs as solo agents and in combination attracted attention at the American Society of Clinical Oncology (ASCO) annual meeting in June.

In the BREAK-3 trial, patients treated with dabrafenib achieved a median progression-free survival (PFS) of 5.1 months compared with 2.7 months for participants treated with dacarbazine, according to results presented at ASCO. The confirmed response rate was 53% with dabrafenib, compared with 19% for dacarbazine.

In the METRIC trial, patients who received trametinib experienced a PFS of 4.8 months compared with 1.5 months for participants who underwent a standard chemotherapy regimen of dacarbazine or paclitaxel.

In another trial, early results from a phase I/II study of various doses of a regimen combining the two drugs indicated patients achieved an overall median PFS of 7.4 months, with the highest PFS achieved in 24 patients who received 150 mg of dabrafenib twice daily and 2 mg of trametinib once daily. For this group, median PFS was 10.8 months, with 15 patients achieving either a partial or complete response.

In addition to the US applications, GSK said it has filed regulatory submissions with the European Medicines Agency for dabrafenib and plans a similar filing for trametinib.