Verastem‘s mesothelioma therapy Defactinib (VS-6063), which a 2016 report said shrank tumors in almost a third of patients in a Phase 2 clinical trial, was featured at the recent 16th Annual Needham Healthcare Conference in New York City.
The therapy is a focal adhesion kinase (FAK) inhibitor. It works by inhibiting FAK, a protein that can impact cancer cells’ ability to spread to other areas of the body. Verastem designed defactinib to reduce the number of the body’s cancerous stem cells, enhance anti-tumor immunity, and modulate the local tumor microenvironment.
Verastem conducted a Phase 2 clinical trial (NCT01870609) of defactinib as a treatment for pleural mesothelioma, a form that starts in tissue called pleura that cover the lungs.
The randomized, placebo-controlled trial compared defactinib and a placebo in patients whose disease had not progressed after four cycles of chemotherapy. The chemotherapy the patients received was a combination of Alimta (pemetrexed) and Platinol (cisplatin) or a combination of Alimta and Paraplatin (carboplatin).
A primary measurement of defactinib’s effectiveness was the number of patients still alive a year after treatment started. Another primary measurement was the time it took for the disease to progress.
A newer clinical trial, the recently completed, open-label, single-center Window of Opportunity study (NCT02004028) tested defactinib before surgery for mesothelioma. Participants received 400 mg of defactinib twice a day for 12, 21, or 35 days. Pre- and post-treatment tissue and blood samples were collected.
The Window trial looked at tumor tissue for biomarker responses to defactinib. It also evaluated the safety of defactinib, the rate of tumor response to the drug, and its pharmakinetics, or ability to move through the body. Researchers evaluated the variables in the Cohort 1 patient group after 12 days of treatment, and in Cohort 2 after 35 days.
Verastem reported in May 2016 that the treatment was well tolerated in the 20 patients in the combined cohorts. It also had no apparent negative impact on surgical outcome, the company said. Six of the 20 patients saw their tumor shrink after treatment. Some were measured 12 days after the therapy and some at 35 days.
The company also reported a correlation between tumor reduction and patients’ ESTIMATE Score, which measures the number of immune cells that infiltrate into tumors. In addition, defactinib increased CD8+ T-cell infiltration and decreased levels of the immunosuppressive cytokine IL-10.
Raphael Bueno, chief of thoracic surgery at Brigham and Women’s Hospital in Boston, presented the results at the 13th International Mesothelioma Interest Group (iMig) Conference May 1-4, 2016, in Birmingham, England.
In addition to mesothelioma, defactinib is being evaluated in combination with immunotherapy as a treatment for pancreatic cancer, ovarian cancer, and non-small cell lung cancer.