Inhibition of mutated, activated BRAF in metastatic melanoma.

ABSTRACT:

Background

The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease.

Methods

We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition.

SUBMITTER: Flaherty KT 

PROVIDER: S-EPMC3724529 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature