Early Results of Clinical Trial for Defactinib Show Promise for Mesothelioma Patients
This article is a correction from the original that inadvertently stated that defactinib was approved by the U.S. FDA. It should have said paclitaxel was approved by the FDA.
In November, MesotheliomaHelp announced the start of the global clinical trial named COMMAND (Control Of Mesothelioma with MAiNtenance Defactinib), to assess the overall survival and progression free survival of mesothelioma patients receiving VS-6063, or defactinib. Last week, Verastem, the maker of the breakthrough drug, announced the early findings of another clinical trial for the drug for ovarian cancer.
According to the company’s press release, of the 22 patients in the United States participating in the clinical trial, 14 (64%) “achieved a best overall response of at least stable disease including two partial responses and two complete responses to date.” Results were presented at the 2014 ASCO Annual Meeting.
In the trial, defactinib was combined with paclitaxel, an anti-cancer drug that is often used in combination with other drugs for various cancers. In a previous study by researchers from the University of Cambridge, paclitaxel was found to have improved efficacy when combined with gemcitabine in treating pancreatic cancer, and potentially other aggressive cancers such as mesothelioma. Paclitaxel was approved by the U.S. Food and Drug Administration in 2012 for use in combination with carboplatin for the initial treatment of patients with locally advanced or metastatic non-small cell lung cancer.
Defactinib targets cancer stem cells that have been shown to survive the effects of anti-cancer drugs allowing them to continue to grow and divide, causing the cancer to metastasize. The drug also targets patients who lack the merlin protein. Merlin is believed to play a role in controlling cell shape, cell movement, and communication between cells. Merlin also functions as a tumor suppressor protein, which prevents cells from growing and dividing too fast or in an uncontrolled way. Mesothelioma tumors that have low levels of merlin are more susceptible to treatment by defactinib, which is known as a focal adhesion kinase (FAK) inhibitor.
FAK is a protein kinase that is critical for cancer stem cell survival. Defactinib slows the activity of the FAK protein, restores the activity of merlin, and thus, slows the growth of cancer cells.
“We believe that to change the way cancer is treated it will be necessary to kill both the cancer stem cells, and the bulk tumor cells, in order to improve patient outcomes for many types of cancer,” said Robert Forrester, Verastem President and Chief Executive Officer, in the press release.
This clinical trial update from Verastem comes on the heels of the release of the company’s study reporting that “the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin.”
According to the report, merlin loss is found in nearly 50 percent of all mesothelioma patients. The researchers found that FAK inhibition effectively reduces cancer stem cells in preclinical models of mesothelioma.
Researchers with GlaxoSmithKline who are testing another FAK inhibitor for mesothelioma patients, GSK2256098, report that when both NF2 and merlin are inactivated, (the NF2 gene provides instructions for the production of merlin), FAK activity increases and mesothelioma cells become invasive and start to spread. When NF2 and merlin activity is restored, FAK activity and cell invasion are decreased.
“These data demonstrate that FAK inhibition is particularly effective in models of merlin-negative mesothelioma,” said Jonathan Pachter, Ph.D., Verastem Head of Research, in the press release announcing the report.