The manufacturer of tazemetostat has now formally begun its planned Phase 2 clinical trial of this novel targeted mesothelioma therapeutic. Tazemetostat is reported to be capable of inhibiting EZH2 activity.
Epizyme, Inc., based in Cambridge, Massachusetts, announced in mid-August 2016 that the first of an expected 67 patients began receiving tazemetostat.
Tazemetostat is designed to be of greatest benefit to mesothelioma patients who have a mutated BAP1 gene. It is estimated that as many as 60 percent of mesothelioma patients have the BAP1 gene mutation.
The clinical trial is being led by researchers at Memorial Sloan Kettering Cancer Center in New York City. However, other cancer centers are also participating. Some are in the U.S.; others are in the United Kingdom and France.
Tazemetostat Clinical Trial for Mesothelioma Patients
Patients enrolled in the clinical trial will receive tazemetostat all by itself. The company has not indicated that it plans to pair tazemetostat with any other drugs during Phase 2.
The clinical trial is starting with just 12 of the 67 patients receiving tazemetostat. This initial dozen will be given an oral dose of 800 mg twice a day.
The remainder of the group will start receiving tazemetostat once the drug’s safety and pharmacokinetic profile are established with the help of those 12 lead patients.
All 67 are slated to continue receiving tazemetostat until at least the primary endpoint of the clinical trial. That will occur after 12 weeks of treatment.
The researchers will then check to see if complete response, partial response or disease stability was achieved.
There are secondary endpoints as well. At each endpoint, the researchers will evaluate overall response rate, progression-free survival, duration of response and overall survival.
The researchers say they are enthusiastic about this clinical trial. One reason for the enthusiasm is they believe tazemetostat may offer hope to patients who relapse after standard chemotherapy – or who don’t respond to chemo at all.
Tazemetostat Inhibits the EZH2 Enzyme
Tazemetostat works by inhibiting EZH2 activity. EZH2 is an enzyme found in healthy cells. However, too much EZH2 is present when the BAP1 gene mutates.
For many mesothelioma patients, the BAP1 gene is believed to mutate as a result of exposure to asbestos fibers trapped in the lungs or intestines.
The resulting overload of EZH2 appears to help mesothelioma cells grow at the out-of-control rate for which this cancer is notorious. In previous lab testing, researchers found it was possible to apply the brakes to mesothelioma cell growth by inhibiting EZH2.
Tazemetostat is designed not only to inhibit EZH2 but also to disrupt mesothelioma cells at the gene level.
The Phase 2 clinical trial comes on the heels of the U.S. Food and Drug Administration designating tazemetostat as an investigational new drug. This designation was granted in May 2016.
The manufacturer is currently conducting Phase 2 clinical trials of tazemetostat for other types of cancers. These include non-Hodgkin lymphoma along with INI1-negative and SMARCA4-negative tumors, and synovial sarcoma.
The company indicates that it wants to also conduct tazemetostat clinical trials in which the drug is paired with atezolizumab for patients with diffuse large B-cell lymphoma.
The manufacturer of tazemetostat is a clinical stage biopharmaceutical company focused on developing novel epigenetic cancer therapeutics.