- Data from the coBRIM study will be presented at an upcoming medical meeting
- Roche plans to submit these data to health authorities around the world
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the Phase III coBRIM study met its primary endpoint. The study demonstrated that the investigational MEK inhibitor cobimetinib, used in combination with Roche's BRAF inhibitor Zelboraf, helped patients with previously untreated BRAF V600 mutation-positive advanced melanoma live significantly longer without their disease worsening (progression-free survival; PFS) compared to Zelboraf alone.1 Adverse events were consistent with those observed in a previous study of the combination.
"Despite great progress in our understanding and therapy in recent years, advanced melanoma remains a difficult and deadly disease that requires more treatment options," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "These encouraging data support the potential combined use of cobimetinib with Zelboraf to block tumour growth longer than Zelboraf alone. We hope this combination therapy will lead to a new option for patients."
Data from this pivotal study will be presented at an upcoming medical meeting. Additionally, Roche plans to submit these data to the U.S. Food and Drug Administration, European Medicines Agency, and other health authorities around the world for potential approval.
Cobimetinib is designed to selectively block the activity of MEK,2 one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival.3 Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumours to grow.4,5
About the coBRIM study
CoBRIM is an international, randomised, double-blind, placebo-controlled Phase III study evaluating the safety and efficacy of cobimetinib in combination with Zelboraf, compared to Zelboraf alone, in 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma, previously untreated for advanced disease.6 The primary endpoint for coBRIM is PFS. Secondary endpoints include overall survival, objective response rate, duration of response and other safety, pharmacokinetic and quality of life measures.6
The coBRIM study used the Roche cobas 4800 BRAF Mutation Test to determine eligibility of patients for the study. This test identifies people whose tumours carry the BRAF V600 mutation, 7 and therefore, patients who are most appropriate to receive this combination of treatments.
Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. BRAF is mutated in approximately half of melanomas.8 When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. More than 232,000 people worldwide are currently diagnosed with melanoma each year,9 and more than 70,000 people worldwide die every year from melanoma and non-melanoma skin cancers.10 In recent years, there have been significant advances in treatment for metastatic melanoma and people with the disease now have more options. However, melanoma continues to be a serious health issue as the incidence has been steadily increasing for the past 30 years.11
Cobimetinib (GDC-0973, XL518) was discovered by Exelixis Inc. and is being developed in collaboration with Exelixis. In addition to the combination with Zelboraf in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumour types, including non-small cell lung cancer and colorectal cancer.
Zelboraf was the first BRAF V600-targeted medicine for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.12 Zelboraf is currently indicated for people with melanoma who carry the BRAF V600 mutation as identified by a validated test such as the cobas 4800 BRAF Mutation Test. It is now approved in more than 80 countries and has been used to treat more than 11,000 patients worldwide.
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, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.
In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
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1.) Roche data on file
2.) Johnston S. XL518, a potent, selective, orally bioavailable MEK1 inhibitor, downregulates the Ras/Raf/MEK/ERK pathway in vivo, resulting in tumor growth inhibition and regression in preclinical models. Poster presented at: AACR-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics; October 22, 2007; San Francisco, CA. Abstract C209.
3.) Khavari TA, Rinn J. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia. Cell Cycle. 2007;6:2928-31
4.) Safaee Ardekani G, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One 2012;7:e47054.
5.) Haferkamp S, et al. Vemurafenib induces senescence features in melanoma cells. J Invest Dermatol 2013;133:1601-9
6.) National Institutes of Health. coBRIM: A Phase 3 Study Comparing GDC-0973 (Cobimetinib), a MEK Inhibitor, in Combination With Vemurafenib vs Vemurafenib Alone in Patients With Metastatic Melanoma. Available at: https://clinicaltrials.gov/ct2/show/NCT01689519?term=cobrim&rank=1 Last accessed June 2014.
7.) McArthur GA, et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014;15:323-32.
8.) Ascierto PA, et al. The role of BRAF V600 mutation in melanoma. J Transl Med 2012;10:85.
9.) WHO. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Last Accessed May 2014.
10.) American Academy of Dermatology. Skin cancer. http://www.aad.org/media-resources/stats-and-facts/conditions/skin-cancer Last accessed May 2014.
11.) American Melanoma Foundation. Skin cancer fact sheet. http://www.melanomafoundation.org/facts/statistics.htm Last accessed July 2014.
12.) Zelboraf Summary of Product Characteristics, February 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002409/WC500124317.pdf Last accessed June 2014