Drugs Xagena
The high degree of selectivity of PLX4032 ( RG7204 ) enables substantial RAF/MEK/ERK pathway inhibition, which may be necessary to achieve significant tumor shrinkage and clinical response in patients with BRAF mutant melanoma.
PLX4032 is a novel, investigational, targeted agent, selective for the oncogenic BRAF mutation prevalent in melanoma and other cancers.
Preclinical studies showed that PLX4032 selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells and causes regression of tumors in BRAF mutant xenograft models. Toxicology studies confirmed a high therapeutic index consistent with a high degree of selectivity.
In the Phase 1 trial, paired biopsy specimens from a subset of patients, were analyzed for pathway inhibition before and after two weeks of treatment. Data showed that with increasing doses of PLX4032, more than 80% inhibition of ERK phosphorylation ( a measure of RAF/MEK/ERK pathway activation ) in the tumors of patients correlated with significant tumor shrinkage and clinical response. In contrast, in patients exposed to plasma levels of PLX4032 at sub-therapeutic doses ( less than 240 mg BID ), partial inhibition of RAF activity in the tumor tissue of a subset of patients did not result in meaningful tumor shrinkage or clinical response.
Melanoma is the most serious type of skin cancer and is growing at a rate of about 5 to 6 percent annually. More than 50,000 people in the United States and 160,000 people worldwide are diagnosed with melanoma each year, which contribute to approximately 48,000 deaths. It is one of the deadliest cancers, with a five-year survival rate of 15 percent. 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 eight months.
Risk factors for melanoma include a family history of melanoma, prior melanoma, multiple clinically atypical moles or dysplastic nevi, 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
XagenaMedicine_2010
