• Data from the coBRIM study will be presented at an upcoming medical meeting;
• Genentech plans to submit these data to the U.S. Food and Drug Administration (FDA).
Genentech, a member of the Roche Group today announced that the Phase III coBRIM study met its primary endpoint. The study demonstrated that the investigational MEK inhibitor cobimetinib, used in combination with Genentech'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. 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 tumor 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, Genentech plans to submit these data to the FDA for potential approval.
Cobimetinib is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumors to grow.
About the coBRIM Study
CoBRIM is an international, randomized, 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. 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.
The coBRIM study used the Roche cobas® 4800 BRAF Mutation Test to determine eligibility of patients for the study. This test identifies people whose tumors carry the BRAF V600 mutation, 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. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. The American Cancer Society estimates there will be more than 76,100 new cases of melanoma and approximately 9,700 melanoma deaths this year in the United States. 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.
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 tumor types, including non-small cell lung cancer and colorectal cancer.
Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal "BRAF" gene. A patient’s healthcare provider will perform a test to make sure that Zelboraf is right for the patient. Zelboraf is not used to treat melanoma with a normal BRAF gene. Zelboraf is now approved in more than 80 countries and has been used to treat more than 11,000 patients worldwide.
Important Safety Information
Zelboraf can cause serious side effects, including risk of cancers. Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC). New melanoma lesions have occurred in people who take Zelboraf. Zelboraf may also cause another type of cancer called non-cutaneous squamous cell carcinoma (SCC). Patients must talk with their healthcare provider about their risk for these cancers. Patients must check their skin and tell their doctor about skin changes including a new wart, a sore or bump that bleeds or does not heal, or a mole that changes size or color.
A patient's healthcare provider should also check for cancers that may not occur on the skin. Patients must tell their healthcare provider about any new symptoms that they get while taking Zelboraf.
While taking Zelboraf, patients should avoid sunlight. When they go outside, patients must wear clothes that protect their skin, including their head, face, hands, arms and legs. Patients must use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.
Possible serious side effects of Zelboraf include severe allergic reactions, severe skin reactions, potentially life-threatening changes in the electrical activity of the heart called QT prolongation, abnormal liver function tests and eye problems. Patients must tell their doctor if they are pregnant or plan to become pregnant as Zelboraf can harm a patient’s unborn baby.
Common side effects of Zelboraf include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching or warts.
Patients must tell their doctor if they have any side effect that bothers them or does not go away. These are not all of the possible side effects of Zelboraf. For more information about side effects, patients should ask their doctor or pharmacist.
Report side effects to the FDA at (800) FDA-1088 or fda.gov/medwatch.
Report side effects to Genentech at (888) 835-2555.
Patients should read the full Prescribing Information and Medication Guide for additional important safety information at zelboraf.com/.
Founded more than 35 years ago, Genentech (gene.com) is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.