Mekinist trametinib: Interim Phase I/II data

Interim data from 147 metastatic melanoma patients with V600 BRAF mutations in an open-label, dose-escalation, U.S. and Australian Phase I/II trial showed that twice-daily 150 mg Tafinlar dabrafenib plus once-daily 2 mg Mekinist led to a median progression-free survival (PFS) of 10.8 months in BRAF inhibitor-naïve patients in part B of the trial (n=24) and 9.4 months in BRAF inhibitor-naïve patients in part C of the trial (n=54). Tafinlar plus Mekinist led to a median PFS of 3.6 months in BRAF inhibitor-resistant patients in both part B (n=26) and part C (n=43) of the trial. In BRAF-inhibitor naïve patients, Tafinlar plus Mekinist led to overall response rates (ORR) of 63% in part B and 76% in part C. In BRAF inhibitor-resistant patients, Tafinlar plus Mekinist led to ORRs of 15% in part B and 9% in part C. All data were from patients who received twice-daily 150 mg Tafinlar plus once-daily 2 mg Mekinist. Part B of the study enrolled cohorts in escalating doses to identify allowable doses to be expanded into the open-label part C. In the part B BRAF inhibitor-resistant group, 93% of patients previously received Tafinlar or vemurafenib and all patients in the part C BRAF inhibitor-resistant group, previously received Tafinlar. Data were presented at the American Society of Clinical Oncology meeting in Chicago.

Last month, FDA approved Tafinlar, an oral BRAF protein kinase inhibitor, to treat melanoma with BRAF V600E mutations as detected by an FDA-approved test. The agency also approved Mekinist to treat melanoma with BRAF V600E or V600K mutations. GSK plans to launch both drugs in the U.S. by early next quarter. MAAs for trametinib as monotherapy, dabrafenib as monotherapy and for the 2 products in combination are under review for melanoma in Europe. GSK said it plans to submit an additional NDA in the U.S. for the combination of the 2 drugs "in the coming months." Alongside the drugs, FDA also approved a PMA from GSK's partner bioMerieux S.A. (Euronext:BIM, Marcy l'Etoile, France) for a companion diagnostic, THxID BRAF test, to detect BRAF V600E and V600K mutations. GSK partnered with bioMerieux in 2010 to develop a companion diagnostic for dabrafenib and trametinib (see BioCentury, May 17, 2010). GSK licensed Mekinist from Japan Tobacco. ...