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Saturday, May 30, 2015

Updated Data Showed Genentech’s Investigational Combination of Cobimetinib and Zelboraf (Vemurafenib) Helps People With Advanced Melanoma Live for a Year Without Their Disease Worsening

Phase III coBRIM study demonstrated a median progression-free survival of 12.3 months with cobimetinib plus Zelboraf

Additional data from Phase Ib BRIM7 study showed 61 percent of people who had not been previously treated with a BRAF inhibitor were alive after two years

The FDA is expected to make a decision on Genentech’s new drug application for cobimetinib in combination with Zelboraf by August 11, 2015

Chicago -- May 30, 2015 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced follow-up data from two studies of the investigational MEK inhibitor cobimetinib in combination with Zelboraf® (vemurafenib). Updated data from the pivotal coBRIM Phase III study showed the combination helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live a median of one year (12.3 months) without their disease worsening or death (progression-free survival; PFS) compared to 7.2 months with Zelboraf alone (hazard ratio [HR]=0.58, 95 percent confidence interval [CI] 0.46-0.72).

"The combination of cobimetinib and Zelboraf extended the time people lived without their disease getting worse to a year," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "These results are exciting because they underscore the importance of combining medicines that target the signals, which cause about half of all melanomas to grow."

The updated results from coBRIM also demonstrated higher response rates with cobimetinib and Zelboraf compared to Zelboraf alone. The objective response rate (ORR) with the combination was 70 percent (16 percent complete response [CR], 54 percent partial response [PR]) compared to 50 percent (11 percent CR, 40 percent PR) in the Zelboraf arm. With further follow-up, the complete response rate increased from 10 percent to 16 percent with the combination as some patients who had a partial response achieved a complete response after more than one year of treatment. The safety profile of cobimetinib and Zelboraf was consistent with safety data previously reported. The most common adverse events in the combination arm were diarrhea, rash, nausea, fever, sun sensitivity, liver lab abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and vomiting.

Follow-up data from the Phase Ib BRIM7 study showed cobimetinib plus Zelboraf helped people who had not been previously treated with a BRAF inhibitor live a median of more than two years (28.5 months). In addition, extended follow-up showed 61 percent of patients who had not been previously treated with a BRAF inhibitor were alive after two years. The safety profile was consistent with the previous analyses. The incidence of serous retinopathy, cardiomyopathy and cutaneous squamous cell carcinoma were similar to those previously reported. 

The coBRIM and BRIM7 data will be presented during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) meeting in Chicago held from May 29 – June 2. CoBRIM data will be presented in an oral session presentation today by Dr. James Larkin, FRCP, The Royal Marsden Hospital, London, UK (Abstract #9006, May 30, 3:15-3:27 P.M. CDT). The BRIM7 data will be presented in a poster presentation by Dr. Anna Pavlick, New York University Medical Center (Abstract #9020, June 1, 1:15-4:45 P.M. CDT). 

The cobimetinib new drug application for BRAF V600 mutation-positive advanced melanoma was granted priority review by the U.S. Food and Drug Administration, and a decision is expected by August 11, 2015. The European Medicines Agency is expected to make a decision on Roche’s marketing authorization application for cobimetinib before the end of 2015.

About the coBRIM study

CoBRIM is an international, randomized, double-blind, placebo-controlled Phase III study evaluating the safety and efficacy of 60 mg once daily of cobimetinib in combination with 960 mg twice daily of Zelboraf, compared to 960 mg twice daily of Zelboraf alone. In the study, 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma (detected by the cobas® 4800 BRAF Mutation Test) and previously untreated for advanced disease were randomized to receive Zelboraf every day on a 28-day cycle plus either cobimetinib or placebo on days 1-21. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent. Investigator-assessed PFS is the primary endpoint. Secondary endpoints include PFS by independent review committee, overall response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures. 

The most common adverse events reported in patients taking cobimetinib in combination with Zelboraf (occurring in more than 20 percent) were diarrhea, rash, nausea, fever, sun sensitivity, liver lab abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and vomiting. Serous retinopathy (collection of fluid under the retina) was observed at a higher frequency in the combination arm (26 vs. 3 percent) with most of these events either Grade 1 or 2, asymptomatic, and temporary in nature. Some adverse events, including cutaneous squamous cell carcinomas and keratoacanthomas, were reported less frequently in the combination arm.

About the BRIM7 study

BRIM7 is a Phase Ib study of 129 patients evaluating the safety and tolerability of cobimetinib in combination with Zelboraf in people with BRAF V600 mutation-positive unresectable or metastatic melanoma who had either not been previously treated with a BRAF inhibitor or had shown disease progression following treatment with a BRAF inhibitor. The primary endpoint of the BRIM7 study focused on safety, tolerability, and the identification of an optimal dose. The secondary outcome measures focused on efficacy. Patients in the dose-escalation stage of the study received cobimetinib 60, 80 or 100 mg once daily given on a schedule of 14 days on/14 days off; 21 days on/7 days off; or continuously for 28 days, and Zelboraf 720 or 960 mg twice daily continuously. Following the dose-escalation stage, two dose levels were selected for further investigation: cobimetinib 60 mg once daily for 21 days on/7 days off and Zelboraf (720 mg or 960 mg twice daily).

The most common adverse events were mild to moderate in severity, and the overall frequency of adverse events with an extended median follow-up of up to 21 months have remained consistent without new safety signals.

About the cobimetinib and Zelboraf combination 

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 cobimetinib 

Cobimetinib (GDC-0973, XL518) was discovered by Exelixis Inc. and is being developed in collaboration with Exelixis. Cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types such as non-small cell lung cancer and colorectal cancer.

About Zelboraf

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. BRAF is mutated in approximately half of melanomas. 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. It is not known if Zelboraf is safe and effective in children under 18 years of age. 

Zelboraf is now approved in more than 90 countries and has been used to treat more than 11,000 patients worldwide. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, now a member of the Daiichi Sankyo Group.

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, liver injury 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 http://www.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 http://www.zelboraf.com.

About melanoma 

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. 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 nearly 74,000 new cases of melanoma and almost 10,000 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 have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.

About Genentech in skin cancer

Genentech has been studying new treatments for skin cancer for nearly 20 years. In the last five years, we have brought two new medicines to people with potentially disfiguring or deadly skin cancers. Genentech is continuing to study our skin cancer medicines as monotherapies and in combination with other investigational medicines, such as cancer immunotherapies, in several cancer types and diseases. 

About Genentech


Founded more than 35 years ago, Genentech 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. For additional information about the company, please visit http://www.gene.com

 

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