Experimental drug PLX4032 holds promise against cancers with faulty BRAF gene....

Plexxikon  recently announced the publication of data from the Phase 1 clinical trial of PLX4032 (RG7204), confirming that treatment of metastatic melanoma patients with the BRAF ^V600E (mutation resulted in significant tumor shrinkage in the majority of patients). The company claims that, in the melanoma extension cohort of the study, nearly all patients showed some response; 81 percent of patients had tumor shrinkage of at least 30 percent and the company concludes that these results further support the current PLX4032 development strategy, which includes parallel and ongoing Phase 2 (BRIM2) and Phase 3 (BRIM3) studies to support registration. PLX4032 is a novel, orally administered, targeted agent that is selective for a key oncogenic driver in melanoma and other cancers. 

Primary objectives of the melanoma extension cohort were to establish further safety and pharmacokinetics (PK) data beyond the dose-escalation phase, as well as demonstrate proof-of-concept in the target patient population at the MTD of 960 mg twice daily.

Results Demonstrate Significant Anti-tumor Activity with PLX4032 . In the melanoma extension cohort, in which 32 patients with metastatic melanoma harboring the BRAF mutation were enrolled, data showed an 81 percent response rate by RECIST criteria, including:  2 complete responses (no evidence of disease) and 24 partial responses (tumor shrinkage of at least 30 percent)

As per the claim by the company, all patients except two showed some tumor regression. The estimated median progression-free survival (PFS) among these patients was at least seven months as of January 31, 2010, compared to historical PFS of less than two months. Sixteen patients were still on study as of January 31, 2010.

Company also claims that, drug-related adverse events were predominantly mild in severity and included rash, joint pain, photosensitivity and fatigue. Among the 48 patients treated in the dose-escalation and extension cohorts, 18 patients developed cutaneous squamous cell carcinoma in sun exposed areas of the skin (primarily keratoacanthoma subtype) that were treated by excision, while treatment with PLX4032 was continued.

This PLX4032 trial represents the first evidence that a treatment that targets activating BRAF mutations can induce significant tumor regressions in patients," said Dr. K. Peter Hirth, CEO  of  Plexxikon. He adds that "these data are particularly encouraging, with responses observed at all sites of disease, including challenging visceral lesions in the bone, liver and small bowel and  they are  hopeful that PLX4032 will provide similar benefit to these patients so urgently in need of effective therapies."..

PLX4032 is currently being tested in a randomized, controlled Phase 3 (BRIM3) trial in previously untreated metastatic melanoma patients who test positive for the BRAF mutation. Enrollment for the trial is currently under way. The primary endpoint for the BRIM3 trial is overall survival....

Ref : http://www.nejm.org/doi/full/10.1056/NEJMoa1002011