A promising new drug for pleural mesothelioma patients, defactinib, is now in phase II clinical trials. Defactinib holds the potential to be the first effective maintenance treatment for mesothelioma patients. Defactinib inhibits the growth of cancer stem cells, preventing metastasis and further growth.

Mesothelioma Guide has been following the development of this promising new drug’s rapid development since September of last year. As part of the global clinical trial of the drug, Verastem is the sponsor of the clinical trial in the U.S.

horobinJoanna Horobin, chief medical officer at Verastem, discussed the future of defactinib in a conference call with the Meso Foundation on Tuesday night.

“I’m more enthusiastic now than I’ve ever been in the last 20 to 30 years,” Horobin said regarding the progress of the study.

To be accepted for the clinical trial, patients must have had at least four cycles of standard chemotherapy treatment. The patient must also have an acceptable performance status, which is essentially overall health. This is important to ensure that any negative side effects were caused by defactinib and not underlying health problems or other drugs. Requirements for acceptable status include being generally healthy and not experiencing too many side effects from the chemotherapy.

In phase I trials, novel drugs are evaluated for their safety and to determine acceptable dosage levels. Phase II trials are designed to test the efficacy of the drug, as well as continuing to monitor its safety.

Now that this study has moved to phase II, a larger group of patients will be accepted to participate. The trial will now begin pulling in data regarding how well the drug works and if it is a viable treatment.

Why Is Maintenance Treatment Important?

Currently there is no standard of care for mesothelioma patients after the first line of therapy. First-line therapy consists of the first rounds of chemotherapy, radiation and surgery. Sometimes this treatment is very effective at removing the cancer.

However, there is no treatment available to prevent the cancer from growing back after the first line of therapy. The science behind defactinib strongly suggests cancer stem cells cause the relapse and spread of mesothelioma.

“In mesothelioma there is particular genetic change that occurs quite frequently in about 40 to 50 percent of patients that makes those tumors possibly more susceptible to one of our cancer stem cell targeting drugs,” said Horobin.

Essentially, the development of an effective maintenance treatment for mesothelioma means survival rates for mesothelioma could increase across the board.

Weeding the Garden

Horobin used a metaphor to explain how defactinib could help mesothelioma patients live much longer. She described a lawn plagued by dandelions that keep growing back despite constant mowing. Chemotherapy can shrink mesothelioma tumors, but cancer stem cells–the dandelions in this metaphor–keep growing back, allowing the tumor to continue growing.

Horobin said that after a patient has chemotherapy “the tumor will eventually come back, so what we want to do is find the dandelion in that tumor, the cancer stem cell, and essentially put weed-killer on it.”

Although defactinib won’t necessarily eradicate tumors, mesothelioma could be managed, preventing the disease from advancing.

Placebo-Controlled Trials Mean Faster Answers

Many patients are understandably concerned about participating in placebo-controlled clinical trials because some of them won’t receive any treatment. Ethical discrepancies can arise from placebo-controlled clinical trials, but these concerns are typically associated with diseases and ailments for which there is an approved treatment.

“In this particular setting, there is no standard of care,” said Horobin.

As it stands, there is no approved maintenance treatment for mesothelioma, much less any drug that has come close to being effective in this setting. Horobin explained how this phase II study may change this reality.

“The real advantage I see, particularly as a drug developer,” said Horobin, “is that if we are lucky enough that this drug actually does produce a benefit in patients with mesothelioma…then take that to the FDA, and other regulatory agencies around the world, they are much more likely inclined to believe the results if the study is being done in a placebo-controlled way.”

This translates into a fast-track toward FDA approval if defactinib proves successful. Furthermore, because there is no maintenance treatment for mesothelioma, patients could feasibly qualify for compassionate use if this study shows a survival benefit. What this means is patients diagnosed with a deadly disease can qualify for the use of unapproved drugs if there are no other treatments available. Drugs issued under compassionate use typically end up being approved later on.

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    About the Writer, Andrew Devine

    Andrew Devine is a contributing writer for Mesothelioma Guide. He has developed an interest in educating patients and their families on everything from new treatments to what to expect after diagnosis.