Date: 2016-06-00
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Roche (Switzerland)
Product: cobimetinib and atezolizumab
Action
mechanism: kinase inhibitor/serine threonine kinase inhibitor/monoclonal antibody/immune checkpoint inhibitor. Cobimetinib (GDC-0973, XL518) was discovered by Exelixis and is being developed in collaboration with Exelixis. The compound is a selective inhibitor of mitogen-activated protein kinase kinase, also known as MEK, a serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK pathway. This pathway mediates signaling downstream of growth factor receptors, and is prominently activated in a wide variety of human tumors. After discovering cobimetinib internally, Exelixis advanced the product to investigational new drug (IND) status. In late 2006, the company entered into its worldwide collaboration with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Following the determination of the maximum tolerated dose in phase 1 by Exelixis, Genentech exercised its option to further develop cobimetinib. Under the terms of the collaboration, Exelixis is eligible to receive royalties on sales of cobimetinib outside the United States. 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. Anti-PDL1 antibody MPDL3280A (atezolizumab) is an investigational monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer.
Disease: colorectal cancer
Therapeutic area: Cancer - Oncology
Country: Australia, Belgium, Canada, Hong Kong, Italy, Poland, Spain, UK, USA
Trial
details: This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy. (NCT02788279)
Latest
news: In June 2016 Genentech initiated COTEZO, a phase 3 pivotal trial of the combination of cobimetinib and atezolizumab in unresectable locally advanced or metastatic colorectal cancer. The trial is expected to enroll 360 patients who have received at least two prior chemotherapies in the metastatic disease setting. The primary endpoint of the COTEZO trial is overall survival.
