Verastem Mesothelioma Clinical Trial Stopped Early For Futility

Illustration of mesothelioma research

Verastem, Inc., a Boston-based biotech company focused on drugs that specifically target cancer stem cells, has stopped its mesothelioma clinical trial early due to futile results in the Phase 2 study of VS-6063.

The study began in 2013 involving almost 400 patients who already exhibited a positive response to the only other existing FDA-approved treatment of mesothelioma cancer—Alimta®. Verastem’s compound, defactinib, was given to half the patients, while the other half received a placebo. The trial was conducted at 35 sites in the U.S., UK, Australia, Canada, South Africa, New Zealand, and Europe.

Defactinib, a focal adhesion kinase (FAK), was thought to work by inhibiting the proliferation of cancer stem cells to prevent several downstream transduction pathways, thus stopping tumor cell migration and survival. The drug was previously proven beneficial in treating patients with ovarian cancer.

Malignant pleural mesothelioma is among the most aggressive and lethal cancers with only one approved therapy,” said Lou Vaickus, MD FACP, Interim Chief Medical Officer. “With the aggressiveness of this disease, the use of single agent VS-6063 as a maintenance treatment following chemotherapy where all patients had residual disease was not sufficient.”

Per a pre-planned interim analysis review done by a Data Safety Monitoring Board (DSMB), the treatment being given to mesothelioma patients post-chemotherapy, wasn’t resulting in “a sufficient level of efficacy” to continue the trial even though VS-6063 had a generally well tolerated safety profile.

“Verastem will be looking at the potential for combination studies, however, we believe VS-6063’s longevity as a drug is now also being called into question,” said Roth Capital’s Joseph Pantgins.

This mid-stage study of mesothelioma was Verastem’s largest one to date, and for its lead therapy in development, but now no more patients will be enrolled in the Phase 2 registration-directed, double-blind, placebo-controlled study (COMMAND). The review indicated VS-6063 was not effective enough to justify the study to move forward. As such, the mesothelioma clinical trial is no longer recruiting.

“We have stopped further enrollment and initiated an orderly wind-down of the COMMAND study,” said Robert Forrester, Verastem President and Chief Executive Officer.

Moving forward, Verastem will use the $132 million it had on hand at the end of the second quarter for VS-4718 and VS-5584 testing on solid tumors, as well as VS-6063 for lung and ovarian cancers.

“There remains a significant unmet need for new treatment options for patients suffering from this very complex, difficult-to-treat cancer,” said Dr. Vaickus. Although VS-6063 will no longer be tested on mesothelioma patients, many other trials are still recruiting if individuals who meet the criteria are interested.

“We are disappointed with the COMMAND outcome, but we are deeply grateful for the support and commitment from the patients participating in the study, their families, and the study investigators. Based on these results, we will reevaluate our clinical priorities and direct our resources toward further development of VS-6063, VS-4718, and VS-5584,” said Forrester.