Press Releases

Plexxikon Publishes PLX4032 Phase 1 Data Demonstrating 81 Percent Response Rate in Metastatic Melanoma Patients in the New England Journal of Medicine

BERKELEY, Calif. – August 25, 2010

Plexxikon today announced 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. Specifically, 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. The data were published in the August 26, 2010 issue of the New England Journal of Medicine, based on an analysis as of January 31, 2010. 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.  

The data published in the New England Journal of Medicine focused on the Phase 1 dose-escalation trial of PLX4032 (RG7204), and a subsequent melanoma extension cohort at the established maximum tolerated dose (MTD). 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)
• 24 partial responses (tumor shrinkage of at least 30 percent)

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.

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 K. Peter Hirth, Ph.D, chief executive officer of Plexxikon. “These data are particularly encouraging, with responses observed at all sites of disease, including challenging visceral lesions in the bone, liver and small bowel. These findings prompted the initiation of two pivotal trials in both second- and first-line melanoma patients. We are hopeful that PLX4032 will provide similar benefit to these patients so urgently in need of effective therapies.”

Accelerated Path to Potential Registration for PLX4032
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. Enrollment was completed earlier this year for the single-arm Phase 2 (BRIM2) trial in previously treated melanoma patients, and data are expected to be presented at a scientific conference later this year. The primary endpoint for the BRIM2 trial is best overall response. Patients interested in enrolling in the Phase 3 trial may find additional information at the Roche Clinical Trials Registry (, at, by visiting, or by contacting the Roche/Genentech Call Center at 888-662-6728.

About PLX4032 (RG7204)—A Personalized Medicine for Cancer Treatment
PLX4032 is a novel, investigational, oral small molecule for melanoma and other cancers harboring the BRAF mutation. Plexxikon utilized its structure-guided chemistry platform to discover PLX4032, and initiated clinical development in 2006. PLX4032 is now being co-developed under a 2006 license and collaboration agreement between Plexxikon and Roche. A DNA-based companion diagnostic to identify patients whose tumors carry the BRAF mutation is being co-developed by Plexxikon and Roche Molecular Systems, Inc. in parallel with the therapeutic development of PLX4032.

About Melanoma
Melanoma is the most serious type of skin cancer and is growing at a rate of about five to six percent annually. More than 50,000 people in the U.S. 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 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.

About Plexxikon
Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s lead compound, PLX4032, is in late-stage clinical trials for the treatment of melanoma. Other clinical-stage programs include PLX5568 for the treatment of polycystic kidney disease, PLX204 for the treatment of diabetes, and PLX3397 for the treatment of metastatic cancer. Among the company’s preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, neuro-inflammatory disorders, multiple sclerosis and other autoimmune diseases as well as for the treatment of other cancers.

Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform integrates multiple state-of-the-art technologies, including structural screening as a key component that provides a significant competitive advantage over other drug discovery approaches. The company has discovered a portfolio of clinical and preclinical stage compounds to address significant unmet medical needs in cardio-renal disease, CNS disorders, inflammatory and neuro-inflammatory diseases, and oncology.