In June, pharmaceutical company Verastem, Inc. announced its investigational drug VS-6063 (now known as defactinib) received orphan medicinal product designation from the European Commission for use in mesothelioma. Now, Verastem is sponsoring a global clinical trial named COMMAND (Control Of Mesothelioma with MAiNtenance Defactinib), which will assess the overall survival and progression free survival of patients receiving the drug.
Mesothelioma, a rare cancer caused by past asbestos exposure, is one of the most aggressive cancers, and one of the most challenging to treat. Although patients are often treated with chemotherapy and radiation, the cancer nearly always returns as the tenacious cancer cells fight mightily to stay alive. Mesothelioma has proven to be resistant to most standard cancer treatments.
Various studies have shown that cancer stem cells can survive the effects of anti-cancer drugs and continue to grow and divide causing the cancer to metastasize. In one study, researchers at the University of Texas Southwestern Medical Center (UT Southwestern) reported that cancer stem cells actually spur regrowth in the tumors. They found that while stem cells build new, healthy cells, they also fuel growth in cancer cells. It is these cancer stem cells that defactinib targets. Experts report that cancer stem cells make up just 1% of cancer cells.
Defactinib is also used to target patients who are low in the Merlin biomarker. Mesothelioma tumors that have low levels of merlin are more susceptible to treatment by focal adhesion kinase (FAK) inhibitors, such as defactinib.
According to ClinicalTrials.gov, Verastem hopes to target 372 malignant pleural mesothelioma patients who have undergone one prior chemotherapy cycle of either pemetrexed/cisplatin or pemetrexed/carboplatin. Patients who have had surgery are also eligible. Any prior treatment of a known FAK inhibitor, however, excludes a patient from participation in the trial. Patients will be treated at sites in 11 countries, including the US, UK, Australia, Canada, South Africa, New Zealand and countries in mainland Europe, according to Verastem.
“There is a large unmet medical need in mesothelioma and an opportunity to develop targeted agents to bring new hope to patients struggling with their disease,” said Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester, incoming President of the International Mesothelioma Interest Group (iMig) and Coordinating Investigator for COMMAND in the UK, at a mesothelioma briefing session with Verastem at the annual American Society of Clinical Oncology meeting in June.
Targeted therapies allow oncologists to offer mesothelioma patients the right treatment at the right time based on the patients’ unique genetic characteristics. Personalized care targeted to the disease’s genetic makeup optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered.
“There is significant enthusiasm within the mesothelioma community for the COMMAND study,” added Fennell.