New Trial COMMAND tests promising new mesothelioma drug

 By Kathy Cooke.    21st November 2013

COMMAND (Control Of Mesothelioma with MAiNtenance Defactinib) is a registration-directed trial of a lead cancer stem cell inhibitor defactinib (VS-6063) in patients with malignant pleural mesothelioma.

Verastem, Inc., the company behind the trial, is a clinical-stage biopharmaceutical company based in the US and their work focuses on discovering and testing new drugs to treat cancer by targeting cancer stem cells.

command mesothelioma trial

Malignant pleural mesothelioma is a highly aggressive form of lung cancer usually associated with exposure to asbestos.

The prognosis of the disease is poor and treatment options which include surgery, radiotherapy and chemotherapy, are usually palliative rather than curative.

One of the reasons for this poor prognosis is that mesothelioma is associated with a high level of cancer stem cells which are resistant to existing treatment options.

The cancer stem cells have proved to be impervious to current Chemotherapy Drugs resulting in progression of the disease and ultimately death.

Although the number of mesothelioma deaths in the UK fell from 2360 in 2010 to 2291 in 2011 (HSE report 2013) there is expected to be an increase in the annual number of deaths peaking at the end of the decade. Approximately 59,000 deaths occur worldwide each year due to mesothelioma (WHO statistics) and so there is a pressing need to develop new treatment options for this group of patients.

During their research Verastem Inc. have found that the focal adhesion kinase (FAK) pathway is critical for the survival of cancer stem cells such as those found in mesothelioma patients. Defactinib (VS-6063), a drug developed by Verastem Inc, is an oral compound designed to preferentially target cancer stem cells through the potent inhibition of FAK.

COMMAND - Control Of Mesothelioma with MAiNtenance Defactinib

COMMAND (Control Of Mesothelioma with MAiNtenance Defactinib) is a new trial of lead cancer stem cell inhibitor defactinib (VS-6063) in patients with malignant pleural mesothelioma; it will be a multi-national trial including 11 countries enrolling around 400 patients with pleural mesothelioma.

The study, devised and lead by Verastem Inc., will be enlisting patients who have undergone a first line treatment currently available for mesothelioma which has been effective in keeping their disease under control but has not destroyed the cancer stem cells and therefore not stopped disease progression. Defactinib will be given after the first line treatment.

Previous research has demonstrated that low merlin levels (a tumour biomarker) are predictive of increased effectiveness of FAK inhibitors such as defactinib. The COMMAND study will therefore subdivide patients to evaluate the effect of defactinib in both the overall patient population and the subgroup that have low merlin levels. Defactinib is currently being used in Phase 1/1b study in ovarian cancer and a Phase 2 trial in KRAS-mutated Non-Small Cell Lung Cancer.

There is “significant enthusiasm within the mesothelioma community” for this drug and we look forward to the update on the progress of this study from Verastem Inc. early next year.

Ref: Verastem Initiates COMMAND: A Registration-Directed Trial of Defactinib in Patients with Mesothelioma, News Release, September 10, 2013, Verastem website.

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