Researchers halted the once-promising clinical trial involving defactinib (VS-6063) and the targeting of malignant pleural mesothelioma stem cells because of the drug's poor performance.
The phase II trial, which began in 2014 with high hopes at 11 different centers across the U.S., stopped enrollment this week following a Data Safety Monitoring Board (DSMB) review of an interim analysis.
That analysis showed VS-6063 was well-tolerated with few side effects, but the level of efficacy was too low, according to Robert Forrester, president and CEO of Verastem, the biopharmaceutical company in Boston producing the drug.
Forrester said 372 patients were enrolled in the trial that spanned across 13 countries.
"Clearly, this is very disappointing," Forrester said during a conference call Tuesday with investors and media. "The study was designed based upon pre-clinical data that predicted greater sensitivity to 6063 in mesothelioma patients. Unfortunately, the hypothesis did not translate clinically."
Ineffective As Maintenance Treatment
The double-blind, placebo-controlled study was known to some as COMMAND, a shortened version of Control Mesothelioma with Maintenance Defactinib. It was scheduled to the end in 2016.
The study was ongoing at cancer centers in:
- New York
- San Francisco
- Cleveland
- Chicago
- Baltimore
- Philadelphia
- Dallas
- Rochester, Minnesota
- Buffalo, New York
- Nashville, Tennessee
- Weston, Florida
Researchers were using Defactinib in this study as a maintenance treatment following chemotherapy on patients with residual disease. The analysis showed little difference between those taking the placebo and those receiving the drug, Forrester said.
"It shows how difficult a patient population this is. Unfortunately, this [mesothelioma] has been a graveyard for drug development," Forrester said. "A single agent in a disease like this is not the right setting for 6063."
More Stem Cell Drugs Coming
Verastem has been testing several new drugs for different cancers that involve inhibiting stem cells, the underlying cause of metastasis and tumor recurrence. Although stem cells are only a small percentage of cells in a tumor, they are considered a major factor in tumor resistance to chemotherapy.
The drugmaker originally believed defactinib could keep mesothelioma patients from relapsing by blocking a signaling pathway within the stem cells.
Defactinib has been effective, and is still being tested with ovarian and non-small cell lung cancers. Forrester said that it likely will be tested again with mesothelioma but in combination with other drugs.
He said the company also would be putting its resources into other mesothelioma drugs being developed. VS-5584 earlier this year was granted orphan drug status by the U.S. Food and Drug Administration, and there are plans to test it in conjunction with defactinib for mesothelioma.
"We need to learn from this," Forrester said. "This is a reminder of how tough mesothelioma is, and how tough biotechnical drug development is. But we still are passionate about our mission, and still believe we can make a difference."
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