Preliminary data from a pivotal phase 2 clinical trial of PLX4032 ( RG7204, Vemurafenib, Zelboraf ) in metastatic melanoma, showing significant tumor shrinkage in the majority of patients, are presented at the seventh annual International Melanoma Research Congress of the Society for Melanoma Research ( SMR ) in Sydney, Australia.
The phase 2 ( BRIM2 ) trial is a single-arm study of previously treated metastatic melanoma patients with the BRAF V600 mutation. Primary endpoints for this study are best overall response rate assessed by an independent review committee ( IRC ) using RECIST criteria, and secondary endpoints are best overall response rate assessed by clinical investigators, duration of response, progression-free survival, overall survival and safety. In pivotal studies, independent review committees are used to review and confirm CT scans, including a second follow-up scan and tumor assessments, allowing a patients response to be characterized as confirmed.
The open-label, multicenter study enrolled 132 patients. As of September 27, 2010, data showed a confirmed response rate of 52%, including: 3 confirmed complete responses ( CR ) ( no evidence of disease ); 66 confirmed partial responses ( PR ) ( tumor shrinkage of at least 30% ).
In addition, 39 patients had stable disease. The median progression-free survival ( PFS ) was 6.2 months, compared to historical PFS of less than two months. The median duration of response was 6.8 months. Median overall survival has not yet been reached.
The unconfirmed response rate in the fhase 2 study was 68 percent, further indicating these data are consistent with the data previously reported from the Phase 1 extension study.
The most common drug-related adverse events were rash, photosensitivity, hair loss and joint pain. These were predominantly mild or moderate in severity. Twenty-six percent of patients developed cutaneous squamous cell carcinoma, which was typically managed without treatment interruption.
Melanoma is the most serious type of skin cancer and is growing at a rate of about 5-6% annually. More than 70,000 people in the U.S. and 160,000 people worldwide are diagnosed with melanoma each year. It is one of the deadliest cancers, with a five-year survival rate of less than 15 percent for people with advanced ( stage IV ) melanoma. Historically, the median progression-free survival for a patient with metastatic melanoma is less than 60 days, and the median overall survival for these patients is approximately 8 months.
Risk factors for melanoma include a positive family history of melanoma, prior melanoma, multiple clinically atypical moles or dysplastic nevi, inherited genetic mutations, fair skin and sun exposure. However, melanoma can occur in any ethnic group and also in areas of the body without substantial exposure to the sun.
Source: Plexxikon, 2010