Exelixis Announces Positive Top-Line Results for Phase 3 Pivotal Trial of Cobimetinib in Combination With Vemurafenib in Patients With BRAF V600 Mutation-Positive Advanced Melanoma
- Study met primary endpoint of significantly improving progression-free survival -
- Data will be presented at an upcoming medical meeting -
- Roche and Genentech plan to submit data to health authorities around the world -
- First of four phase 3 data sets for Exelixis-discovered compounds expected in 2014 -
Exelixis, Inc.
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- 14th July
Exelixis, Inc. (EXEL) today announced positive top-line results from coBRIM, the phase 3 pivotal trial evaluating cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma harboring the BRAFV600 mutation. Exelixis’ collaborator Genentech, a member of the Roche Group, informed the company that coBRIM met its primary endpoint, delivering a statistically significant increase in progression-free survival (PFS) for the combination of cobimetinib plus vemurafenib as compared to vemurafenib alone. Adverse events were consistent with those observed in a previous study of the combination. Genentech will present these coBRIM data at an upcoming medical meeting and plans to initiate regulatory filings before year end.
“These positive top-line results from coBRIM represent an important milestone for melanoma patients and their physicians, and are the first of four anticipated phase 3 pivotal trial read-outs for Exelixis-discovered compounds in 2014,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “Despite recent therapeutic innovations, BRAFV600 mutation-positive advanced melanoma can be difficult to treat due to the emergence of resistance. We look forward to the full presentation of the data later this year. If ultimately approved, we will execute on our collaborative U.S. co-promotion effort with Genentech and work alongside our partner to bring this important new therapeutic option to melanoma patients in need.”
In addition to the coBRIM results just announced, Exelixis anticipates delivering on the following key clinical development initiatives before the end of 2014:
Top-line results from pivotal phase 3 studies COMET-1 (overall survival endpoint) and COMET-2 (pain palliation endpoint) of cabozantinib in metastatic castration-resistant prostate cancer;
Top-line results from the overall survival analysis of EXAM, the phase 3 pivotal trial of cabozantinib in progressive, metastatic medullary thyroid cancer; and
Completing enrollment in METEOR, the phase 3 pivotal trial of cabozantinib in metastatic renal cell cancer.
About the Phase 3 Pivotal Trial coBRIM
coBRIM is an international, randomised, double-blind, placebo-controlled phase 3 study evaluating the safety and efficacy of cobimetinib in combination with vemurafenib, compared to vemurafenib alone, in 495 patients with BRAFV600 mutation-positive unresectable locally advanced or metastatic melanoma, previously untreated in the metastatic setting. The primary endpoint for coBRIM is progression-free survival. Secondary endpoints include overall survival, objective response rate, duration of response, and other safety, pharmacokinetic and quality of life measures.
About the Collaboration
Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the end of phase 1, at which point Genentech exercised its option to further develop the compound.
In November 2013, Exelixis exercised its option to co-promote cobimetinib, if approved, in the United States. Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States.
About the Combination of Cobimetinib and Vemurafenib
Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK pathway) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50% of tumors. Tumors with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor. In preclinical melanoma models, co-treatment with vemurafenib and the MEK inhibitor cobimetinib may delay the emergence of resistant tumors. In addition to the combination with vemurafenib 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. |
