Roche reports promising Phase II results with new targeted approach in advanced melanoma

RocheRoche (SIX: RO, ROG; OTCQX: RHHBY) announced results from a Phase II clinical study of RG7204 (PLX4032), an investigational first-in-class molecule designed to selectively inhibit a cancer-causing, mutated form of the BRAF protein found in approximately half of metastatic melanoma tumors. The open-label study, known as BRIM2, showed that the BRAF inhibitor RG7204 shrank tumors in more than half of people with previously treated BRAF V600E mutation-positive metastatic melanoma. People who participated in the trial lived a median of 6.2 months without their disease getting worse (median progression-free survival or PFS). Typically, progression-free survival for these patients is approximately two months and median overall survival is six to nine months.

The data were presented at the seventh International Melanoma Research Congress of the Society for Melanoma Research in Sydney, Australia by Jeffrey Sosman, M.D. on Friday, November 5, 9:00 a.m. AEDT.

"We are pleased by the RG7204 study results in advanced melanoma, one of the top causes of cancer deaths in young adults," said Dr. Sosman. "We now have additional data that confirm promising clinical activity in previously treated patients with BRAF V600E mutation-positive metastatic melanoma."

"We are very encouraged by these data and based on the Phase II findings we are working to open an expanded access program. This would make RG7204 available to people with BRAF-mutation positive advanced melanoma who have had at least one prior medicine," explained Hal Barron, M.D., Head of Global Product Development and chief medical officer. "People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this therapy to people with this type of cancer."

RG7204 exemplifies Roche’s personalized healthcare approach using biomarkers and diagnostic tools to identify the right medicine for the right patient. RG7204 is being co-developed with a diagnostic test from Roche Molecular Diagnostics to identify patients whose tumors carry the mutated BRAF gene and are therefore most appropriate for treatment.

About BRIM2
BRIM2 is a single-arm, multi-center, open-label Phase II study that enrolled 132 patients with previously treated BRAF V600E mutation-positive advanced melanoma. Mutation status was determined by the cobas 4800 BRAF V600 Mutation Test, a Roche Molecular Diagnostics companion diagnostic assay being co-developed with RG7204. Study participants received RG7204 twice daily until disease progression. The primary endpoint of the study was ORR as assessed by an independent review committee. Secondary endpoints of the study included duration of response, PFS, and overall survival. Of the 132 patients who received RG7204, results showed:

  • 52 percent of patients had tumors decrease in size by 30 percent or more for at least two consecutive scans as assessed by an Independent Review Committee.
  • 82 percent of patients had either a response or stable disease (52 percent responders plus 30 percent stable disease)
  • People who participated in the trial lived a median of 6.2 months without their disease getting worse (median progression-free survival or PFS).
  • Median duration of response was 6.8 months.
  • Median overall survival has not yet been reached.
  • The safety profile was generally consistent with previous RG7204 clinical studies. In the study, the most severe (Grade 3 or greater) adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and gastrointestinal (dysphagia/pancreatitis) (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain.
  • Also reported was Grade 3 cutaneous squamous cell carcinoma (cSCC), a type of skin cancer in 26 percent (34/132) percent of patients. In cases of cSCC, the lesions were excised and the patients continued with treatment. The incidence of cSCC was consistent with that observed in a previous study of RG7204.

About Advanced Melanoma and BRAF
Advanced melanoma is the deadliest and most aggressive form of skin cancer. A person with advanced melanoma typically has a short life expectancy that is measured in months. Less than one in four people are expected to be living one year after diagnosis and every year there are an estimated 40,000 deaths worldwide from the disease.(1) The number of people with melanoma in developed countries is predicted to double over the next decade from 138,000 new cases a year to 227,000 new cases by 2019.(2) Until recently there has been no major advance in treatment for 30 years and patients with advanced melanoma have had very few treatment options.

The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Activating mutations in the BRAF gene cause this pathway to be overactive, which may lead to excessive growth and cancer. Mutations in the BRAF V600 protein are found in about 50 percent of melanomas and it is estimated that approximately eight percent of all solid tumors contain BRAF V600 mutations.

About RG7204
RG7204 is an investigational, oral, small molecule that is designed to selectively inhibit a cancer-causing mutated form of the BRAF protein. RG7204 is being co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon. A polymerase chain reaction-based companion diagnostic, the cobas® 4800 BRAF V600 Mutation Test, is being co-developed by Roche Molecular Diagnostics and Plexxikon in parallel to identify people whose tumors carry the BRAF V600E mutation.

A Phase III study (BRIM3) of RG7204 in previously untreated metastatic melanoma patients whose tumors test positive for the BRAF V600 mutation by the companion diagnostic test is currently ongoing. Additional information about the clinical trials is available at the Roche Clinical Trials Registry (http://www.roche-trials.com).

About SMR2010
The Society for Melanoma Research (SMR2010) is the most comprehensive melanoma conference of the decade. The combination of 4 independently structured and integrated meetings has allowed the evolution of concise programs, each oriented to a specific audience, providing great opportunities for cross specialty exchange of knowledge and ideas.

The overall Congress theme is 'Pathways to Treatment', which encompasses the ongoing translation of our basic knowledge of the cellular pathways underlying melanoma development to the design of new molecular therapies to treat this disease. A broad interdisciplinary program highlights cutting edge developments in primary and secondary prevention of melanoma.

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74–108.
2. Data Monitor Report. Stakeholder Opinions: Melanoma - Future treatment will be based on individual tumor gene expression signatures, 2010.

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