Data from Phase 2 Study of Pre-surgery Treatment in MPM Patients Presented at iMig 2016

Data from Phase 2 Study of Pre-surgery Treatment in MPM Patients Presented at iMig 2016

Dr. Raphael Bueno, chief of Thoracic Surgery at Brigham and Women’s Hospital (BWH) in Boston, recently presented clinical data of the ongoing, Verastem-sponsored Phase 2 clinical trial of a neoadjuvant treatment in people with malignant pleural mesothelioma who are eligible for surgery

Dr. Bueno’s oral presentation, given at the 13th International Mesothelioma Interest Group (iMig) Conference held May 1-4 in Birmingham, U.K., was titled “Phase 2 Neoadjuvant Study of VS-6063, a FAK Inhibitor, in Subjects with Surgically Resectable Malignant Pleural Mesothelioma.

The open-label and single-center “Window of Opportunity” study (NCT02004028) is investigating the treatment VS-6063 in patients prior to mesothelioma surgery. Participants received VS-6063 (defactinib) 400 mg twice daily for 12, 21, or 35 days. Pre- and post-treatment biopsies and blood samples are being collected. VS-6063 is an inhibitor of the focal adhesion kinase (FAK), which is known to be involved in cellular adhesion and in cancer’s metastatic capability. VS-6063 was designed to reduce cancer stem cells, enhance anti-tumor immunity, and modulate the local tumor microenvironment.

The study’s purpose is to assess biomarker responses from tumor tissue, as well as the safety, pharmacokinetics, and tumor response rate to defactinib therapy. These variables are being evaluated following either 12 days (Cohort 1) or 35 days (Cohort 2) of treatment.

Results showed that patients in Cohort 1 and Cohort 2 (n=20) well tolerated treatment with VS-6063, with no apparent negative impact on surgical outcome. Six of the 20 had tumor reduction after receiving VS-6063 for 12 or for 35 days. There was a positive correlation between tumor reduction and an ESTIMATE Score (Estimation of STromal and Immune cells in Malignant Tumours). Treatment with VS-6063 resulted in increased CD8+ T-cell infiltration, and a decrease in the immunosuppressive cytokine IL-10.

“Results from this early-stage study show that single-agent VS-6063 was generally well tolerated as a neoadjuvant therapy in chemotherapy-naïve patients,” Dr. Bueno said in a recent press release. “In addition to evidence of a favorable safety profile, we also observed reductions in tumor size and favorable potential immunomodulatory effects. These Cohort 2 results continue the findings from Cohort 1 for the effects of single-agent VS-6063 in surgically-eligible mesothelioma patients.”

“These data are early but encouraging, and support the growing body of research supporting the thesis that FAK inhibition produces favorable changes within the tumor microenvironment,” added Gregory Berk, chief medical officer of Verastem.

Eligible patients are still being recruited to take part in the study; information is available through this link.

Malignant pleural mesothelioma is a rare, aggressive cancer that develops in the thin layer of tissue surrounding the lungs, known as the pleura. The disease is caused primarily by the inhalation of microscopic asbestos fibers. Once these fibers are inhaled, they can become lodged in the lining around the lungs, and cause cellular and genetic damage, which can ultimately lead to cancer. It is the most common of the four types of mesothelioma, accounting for about 75 percent of all cases diagnosed annually in the U.S. More than 2,000 people are diagnosed with this pleural cancer each year.


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