Plexxikon updates Zelboraf Phase 1 data on BRAF V600E mutation-positive melanoma

Nov 8 2012

Plexxikon today announced that updated Phase 1 clinical data of Zelboraf^® (vemurafenib) were presented at the Society for Melanoma Research (SMR) 2012 Congress, held November 8-11 in Los Angeles, CA. These data represent the longest follow-up of any cohort of patients treated with any BRAF inhibitor. The data show that 26 percent of patients were alive at three years suggesting that long-term survival with Zelboraf can be achieved in a subset of metastatic melanoma patients with the BRAF V600E mutation.

The Phase 1 extension study, which was conducted by Plexxikon and Plexxikon's partner Roche, included 32 patients with BRAF V600E mutation-positive melanoma. As of July 17, 2012, the date of the analysis, the data showed:

• Long-term overall survival:

55% of patients were alive at 1 year
36% of patients were alive at 2 years
26% of patients were alive at 3 years

• Progression-free survival (PFS) benefit:

Median PFS of 7.7 months

Five patients remain on vemurafenib to date, three of whom continue to have complete responses with no evidence of disease and one of whom continues to have a partial response.

Data also suggest a potential benefit of vemurafenib's use in conjunction with post-progression surgery, as well as continued drug administration in some patients with isolated melanoma metastases. Fourteen of the 32 patients received vemurafenib post-progression.

The most common drug-related adverse events in this Phase 1 study were joint pain, rash, nausea, sun sensitivity, fatigue, cutaneous squamous cell carcinoma, itching and hand-foot syndrome.

"Plexxikon is pleased to report the results from this study, which demonstrate that long term survival was achieved in a subset of patients," said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. "Since initiating the first clinical trial in 2006, our primary goal has been to provide a new treatment option for metastatic melanoma patients with the BRAF V600E mutation who historically have had very limited treatment options."

Other Zelboraf Clinical Trial Results Continue to Mature

Zelboraf was approved by FDA in August 2011, following positive results of an interim analysis of BRIM3, a global, randomized, open-label, controlled Phase 3 study that compared Zelboraf to dacarbazine (chemotherapy), in 675 patients with previously untreated BRAF V600E mutation-positive, unresectable (inoperable) or metastatic melanoma. The BRIM3 study met the specified criteria for co-primary endpoints of overall survival and progression-free survival in January 2011. The risk of death was reduced by 56 percent for patients who received Zelboraf compared to those who received chemotherapy ((hazard ration [HR]=0.44, p<0.0001). Median overall survival of patients receiving Zelboraf had not been reached, and was 7.9 months for those receiving chemotherapy. There were 78 deaths and 121 deaths in the Zelboraf and dacarbazine arms, respectively. Median PFS was 5.3 months for those who received Zelboraf compared to 1.6 months for those who received chemotherapy (HR=0.26, p<0.0001).

In June 2012, updated results from the BRIM3 study were reported at the 48^th Annual American Society of Clinical Oncology (ASCO) Meeting. In an analysis of BRIM3 data with a longer follow-up compared to previous analyses, including crossover of patients from the chemotherapy treatment arm to the Zelboraf treatment arm, Zelboraf improved survival by providing a median overall survival of 13.6 months compared to 9.7 months in those who received chemotherapy. The risk of death in patients receiving Zelboraf was reduced by 30% compared to those receiving chemotherapy (HR=0.70, p<0.001). Until recently, patients with metastatic melanoma could only expect to live for six to nine months after diagnosis.

In February 2012, updated results from the BRIM2 trial, a single arm, multi-center Phase 2 clinical study of vemurafenib in patients with previously treated V600E BRAF mutation-positive metastatic melanoma, were published in the New England Journal of Medicine. The study demonstrated that patients who were treated with vemurafenib had a median overall survival of 15.9 months, compared with historical survival of nine months with conventional treatment. At 12 months, 58 percent of patients treated with vemurafenib were still alive.

Source: Plexxikon