- Cobimetinib plus Zelboraf reduced the
risk of disease worsening by half compared to Zelboraf alone
- Phase III coBRIM study results will be
presented today during the Presidential Symposium at the European
Society of Medical Oncology (ESMO) 2014 Congress and published in
the New England Journal of Medicine
- Roche has submitted a European Union
marketing authorization application for the combination for the
treatment of BRAF V600 mutation-positive advanced melanoma
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX:
RHHBY), today announced positive data from the coBRIM Phase III
study. The results showed that people with previously untreated
BRAF V600 mutation-positive advanced melanoma who received the MEK
inhibitor cobimetinib plus Zelboraf® (vemurafenib) lived
significantly longer without their disease worsening or death
(progression-free survival; PFS) compared to Zelboraf alone.
The combined therapy reduced the risk of disease worsening or
death by half (hazard ratio [HR]=0.51, 95 percent confidence
interval [CI] 0.39-0.68; p<0.0001), with a median PFS of 9.9
months for cobimetinib plus Zelboraf compared to 6.2 months with
Zelboraf alone. The safety profile was consistent with a previous
study of the combination. The most common adverse events seen in
the combination arm included diarrhea, nausea, rash,
photosensitivity and lab abnormalities.
“We combined cobimetinib and Zelboraf in this study to better
inhibit a major cancer growth pathway and hopefully improve
clinical outcomes,” said Sandra Horning, M.D., chief medical
officer and head of Global Product Development. “The coBRIM results
are exciting because they support the potential of the combination
as a new treatment option for people with BRAF mutation-positive
advanced melanoma.”
The coBRIM results were statistically significant across
multiple secondary endpoints. The median PFS by independent review
committee (IRC) was 11.3 months for the combination arm compared to
6.0 months for the control arm (HR=0.60, 95 percent CI 0.45-0.79;
p=0.0003). The objective response rate (ORR) was higher in the
combination compared to the control arm (68 vs. 45 percent;
p<0.0001). Overall survival (OS) data are not yet mature.
The late-breaking coBRIM data will be presented at ESMO 2014
today during the Presidential Symposium by Professor Grant
McArthur, Peter MacCallum Cancer Centre, Australia (Abstract
#LBA5_PR, Monday, September 29, 2014, 4:00-5:20 p.m. CEST) and are
also part of the official press program. Additionally, the study
was published online today in the New England Journal of
Medicine.
Roche has submitted the coBRIM data to the European Medicines
Agency, and Genentech plans to submit a New Drug Application to the
U.S. Food and Drug Administration later this year.
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 was the primary endpoint. In
addition to PFS by IRC, ORR and OS, secondary endpoints included
duration of response and other safety, pharmacokinetic and quality
of life measures.
There was a higher overall frequency of Grade 3 or higher
adverse events in the combination arm (65 vs. 59 percent), with
close to half of these due to lab abnormalities. Common adverse
events (occurring in more than 20 percent) observed at a higher
frequency (all grades) in the combination arm compared to the
Zelboraf arm included diarrhea (57 vs. 28 percent), nausea (39 vs.
24 percent), photosensitivity (28 vs. 16 percent), lab
abnormalities (increased alanine aminotransferase [24 vs. 18
percent], increased aspartate aminotransferase [22 vs. 13 percent],
increased creatine phosphokinase [an enzyme released by muscles, 30
vs. 3 percent]) and vomiting (21 vs. 12 percent). Common adverse
events observed at a lower frequency in the combination arm
included hair loss (14 vs. 29 percent), thickening of the outer
layer of the skin (10 vs. 29 percent) and joint pain (33 vs. 40
percent). Most instances of each common adverse event were Grade 1
or 2 in severity.
Other select adverse events that were lower in the combination
arm included cutaneous squamous cell carcinomas (3 vs. 11 percent;
all grades) and keratoacanthomas (<1 vs. 8 percent; all grades).
Serous retinopathy (collection of fluid under the retina) was
observed at a higher frequency in the combination arm (20 vs. <1
percent) with most of these events either Grade 1 or 2 and
temporary in nature. Specific adverse events leading to withdrawal
from treatment were similar in both study arms, as was the overall
discontinuation rate from treatment (13 vs. 12 percent).
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 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 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 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. Zelboraf is now approved in more
than 80 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, 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
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 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.
GenentechMedia Contact:Emmy Wang, 650-467-6800Advocacy
Contact:Sonali Chopra, 650-467-0842Investor Contacts:Eka
Kortkhonjia, 650-467-5873Karl Mahler, 011 41 61 687 8503
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