On October 24, 2014, at the iMig (
International Mesothelioma Interest Group) Conference, Professor Raphael Bueno, M.D., Chief of Thoracic
Surgery, Brigham and Women’s Hospital (BWH), presented preliminary data
on Verastem, Inc.’s clinical ‘Window of Opportunity’
study evaluating the biomarker response to VS-6063 (defactinib), an oral
small molecule that targets cancer stem cells through the inhibition of
focal adhesion kinase (FAK) in pleural mesothelioma patients (mpm) eligible
for resection surgery.
The drug was administered to 10 patients twice a day, for 12 days, with
biopsies performed before and after the administration of the drug. Tumor
size was measured using CT/
PET scans before and after the 12-day administration of VS-6063.
VS-6063 reduced FAK activity by an average of 70%, and in 5 of the 7 patients
reduced the presence of cancer stem cell markers in the post-treatment
biopsies. None of the 10 patients saw any tumor growth in the 12 days,
and 2 of the 10 patients experienced partial tumor shrinkage of -30%, and -49%.
“To follow up on these encouraging results, the protocol is being
amended to explore more extended dosing in 10-15 additional patients with
mesothelioma prior to surgery,” said Dr. Bueno. “The window
of opportunity before elective surgery provides a novel platform for the
clinical evaluation of promising new agents for the treatment of this
In addition to the ‘Window of Opportunity’ study, Verastem
is conducting a registration-directed COMMAND (Control Of Mesothelioma
with MAinteNance Defactinib) study as a disease maintenance program following
successful treatment with Alimta and cisplatin in patients with mpm.
Verastem also presented preclinical data at the iMig Conference which demonstrated
the ability of VS-6063 and the combination of VS-6063 and VS-5584 to target
and kill cancer stem cells in models of mesothelioma.
The administration of drugs prior to surgery to suppress tumor growth is
not new. Many patients undergo
chemotherapy before surgery in an effort to reduce tumor size and minimize complications.
The possibility of inhibiting the disease’s production of a particular
biomarker linked directly to tumor growth is very promising.
Verastem’s approach to developing targeted therapies for mesothelioma
has the potential to not only improve treatment of this aggressive and
deadly disease, but to offer new hope to patients struggling with their disease.