Plexxikon and Roche Report Positive Data from Phase III BRAF Mutation Melanoma Study

Partners Plexxikon and Roche reported positive data from a placebo-controlled open-label Phase III study evaluating vemurafenib in patients with previously untreated BRAF v600 mutation-positive locally advanced or metastatic melanoma. Key data from the 675-patient BRIM3 study showed that in comparison with dacarbazine chemotherapy, treatment using vemurafenib prolonged survival and increased the proportion of patients achieving tumor shrinkage. Trial participants were enrolled on the basis of their BRAF mutation status, assessed using the investigational cobas 4800 BRAF V600 Mutation Test that Roche and Plexxikon are developing in parallel with vemurafenib.

More specifically, the response rate (measured as tumor shrinkage) was 48.4% among vemurafenib patients, compared with 5.5% for chemotherapy-treated patients. Eighty-four percent of vemurafenib-treated patients were still alive after six months, compared with 64% of patients receiving chemotherapy. Median progression-free survival was 5.3 months for the vemurafenib treatment arm, compared with 1.6 months for patients in the chemotherapy cohort. Announcement of the BRIM3 data at the American Society of Clinical Oncology Annual Meeting coincided with their publication in NEJM.

The firms stress that median overall survival can’t yet be reliably estimated because of the small number of patients in long-term follow-up. Median overall survival estimates when BRIM3 met its primary co-primary endpoint in January 2011 were 9.2 months for patients receiving vemurafenib and 7.8 months for those receiving chemotherapy. After an additional two months of follow-up, the estimated median overall survival was 10.5 months for patients receiving vemurafenib, and again 7.8 months for chemotherapy-treated patients.  

In January the data safety monitoring board for the BRIM3 trial recommended terminating the study due to the positive efficacy data in order to allow enrolled patients in the chemotherapy arm to start receiving vemurafenib. Marketing applications for approval of vemurafenib in the treatment of BRAF v600 mutation-positive melanoma have been submitted to FDA and the European Medicines Agency. While still under regulatory review, the drug is being made available to eligible patients through a global access program.

Vemurafenib is an oral small molecule drug originating from Plexxikon’s in-house research. The firm’s co-development deal for the drug with Roche was signed back in 2006. The latter says it is pursuing a broad development program for vemurafenib in multiple tumor types, including combination regimens with both approved and developmental drugs.

Just three days ago Plexxikon announced the start of new vemurafenib clinical trials. These include a clinical study combining vemurafenib with an oral MEK kinase inhibitor GDC-0973 in BRAF v600 mutation melanoma patients, and a Phase II monotherapy study in refractory papillary thyroid cancer patients. A study combining vemurafenib with an immunologic antibody infusion therapy is also being planned for the metastatic melanoma indication.