Tazemetostat Shows Promise for Pleural Mesothelioma

Five different research groups at the American Society of Clinical Oncology annual meeting last month made presentations on the effectiveness of tazemetostat, a novel protein inhibitor, in fighting various cancers.

Pleural mesothelioma was one of those cancers in which clear efficacy was demonstrated, raising hopes again for a future second-line therapy option.

“It wasn’t the breakthrough you may be looking for, but there is a set of patients now that can benefit from this treatment for a period of time,” Dr. Marianna Koczywas, medical oncologist at City of Hope cancer treatment and research center in California, told The Mesothelioma Center at Asbestos.com. “It was a step in the right direction.”

City of Hope was one of seven treatment centers within the United States that conducted the phase II clinical trial. UCLA Medical Center, University of California-San Francisco Cancer Center, Dana-Farber Cancer Institute in Boston, Massachusetts General Hospital, Mayo Clinic in Rochester, Minnesota, and Memorial Sloan Kettering Cancer Center in New York City also participated.

Several centers in France and the United Kingdom also played host to the mesothelioma clinical trial.

“The drug is promising,” Koczywas said. “Findings from this trial, though, need further exploration for malignant mesothelioma.”

Finding Molecular Targets for Tazemetostat Treatment

Tazverik is the brand name of tazemetostat. It is a targeted therapy that works by blocking the enzyme EZH2, which inhibits the genes that normally would suppress cancer tumor growth.

Previous studies have shown tazemetostat is more effective where the BAP1 tumor suppressor gene is mutated, which happens in more than 60% of patients with pleural mesothelioma.

The mutation of BAP1 normally leads to higher expression of EZH2, which leads to accelerated cancer growth that can be reduced with tazemetostat.

Earlier research also has shown that those with a BAP1 gene mutation are more likely to develop mesothelioma, but it makes them more receptive to therapy.

“The key is identifying patients where tumors are sensitive to this targeted therapy,” Koczywas said. “What is driving the cancer growth, you try to block it at the molecular level.”

The two-part trial began with 74 patients with relapsed or refractory pleural mesothelioma, including 70 with the BAP1 gene mutation investigators were seeking. They were enrolled initially between 2016 and 2018. Trial cutoff date was Feb. 20, 2020.

Tazemetostat was taken orally twice each day. The second part of the trial was its most effective, with 61 patients with BAP1 mutation participating.

The disease control rate was 54% and 33% at 12 and 24 weeks, respectively. Disease control rate is defined as either stable disease, complete response or partial response. Stable disease was found in 62% of patients at 12 weeks.

Median progression-free survival was 18 weeks and median overall survival was 36 weeks. Two patients showed a durable response for up to 30 weeks.

Less than 5% of the patients in the trial had serious side effects. The most common were shortness of breath and anemia.

Tazemetostat Already Used with Other Cancers

The U.S. Food and Drug Administration approved the use of tazemetostat earlier this year for patients with relapsed or refractory lymphoma and high expression of EZH2.

Accelerated approval was also granted by the FDA for adult patients with certain types of unresectable epithelioid sarcoma.

Epizyme Inc., which produces the tazemetostat, is a clinical stage biopharmaceutical company promoting the drug as a second-line therapy for different cancers.

Standard-of-care treatment for mesothelioma typically involves a combination of chemotherapy, surgery and radiation, but the effectiveness has been limited. Less than one-fourth of patients even qualify for surgery.

There are no FDA-approved second-line therapies for mesothelioma, but several are being moved through the approval process. Tazemetostat is among those.

“At this stage, there is nothing out there to cure mesothelioma,” Koczywas said. “We’re trying to find a way to manage it, control disease and lengthen survival.”

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