Early results from an international clinical trial involving the targeted killing of mesothelioma stem cells are better than anticipated, fueling considerable hope for the future of treatment.
The phase II trial of the drug defactinib (VS-6063) currently includes 180 patients enrolled at 55 sites in 13 countries. Verastem, Inc., a relatively small biopharmaceutical company based in the Boston area, markets the drug.
The drug also is being tested – with equally encouraging results – for ovarian and non-small-cell lung cancers.
“We’re onto something really important here,” Verastem president and Chief Financial Officer Robert Forrester said. “We believe we have the opportunity to change the way cancer is treated and to make a significant difference in the lives of many patients.”
Forrester spoke earlier this month on a conference call detailing the company’s 2014 accomplishments and its plans for the future.
Verastem is testing a handful of its own novel drugs for different cancers, but all involve the killing of stem cells, which are the underlying cause of tumor recurrence and metastasis.
“Our confidence in each of these drugs continues to grow,” he said. “The outlook has been grim for a patient with mesothelioma. The good news is that targets in treatment are clearly emerging. There is increasing confidence now that 6063 is a drug that can help many patients. We’ve seen what is happening.”
Mesothelioma stem cells represent only a small percentage of cells in a tumor, but they are a major cause of tumor resistance to chemotherapy.
Defactinib is designed to obstruct Focal Adhesion Kinase (FAK), a specific protein within stem cells. When that happens, the cancer loses its capacity to grow. Some scientists believe chemotherapy alone, while initially shrinking a tumor, increases the number of stem cells and leads to metastasis.
Patients commonly refer to the study as COMMAND, a shortened version of Control of Mesothelioma with Maintenance Defactinib. Defactinib is administered along with Alimta (pemetrexed), the only FDA-approved drug for the treatment of mesothelioma.
Verastem Chief Medical Officer Dr. Joanna Horobin said trial sites are reporting few side effects and surprisingly good patient response to the drug. The study expects to have its targeted goal of 372 patients enrolled by the end of 2015. It could finish in 2016.
“The goal is to try and improve disease control,” Horobin said. “The signals of clinical activity and long-term tolerability are encouraging. We’re seeing improved patient quality of life.”
Dr. Raphael Bueno, chief of thoracic surgery at Brigham and Women’s Hospital, reported the early findings at the International Mesothelioma Interest Group Conference last fall in South Africa.
“This [VS-6063] is not only an opportunity, but a responsibility to patients because we’ve maximized the efficiency of surgery and chemotherapy,” Bueno said. “I think we demonstrated we could give this drug safely and get a reasonable response. Something worked.”
As part of the study, researchers previously had tested VS-6063 as a pre-surgery drug for mesothelioma patients at Brigham and Women’s Hospital.
Patients were given the drug for 12 days prior to surgery, and tumor size shrunk in 70 percent of the patients. The treatment period in that study has since been expanded to 35 days.
The study also has shown the drug is more effective for patients who lack a protein called merlin. The study found that 41 percent of the patients fell into that category, which could provide a more precise target in the future and where it will work best.
“Our hope is to have 6063 approved ASAP. Mesothelioma is the right tumor for that,” Forrester said. “Our goal is to achieve the first approval in mesothelioma, and then broaden its use to many major cancers, like lung, ovarian and breast cancers.”
Researchers are still recruiting clinical trial patients in the following U.S. cities: