Rare Disease Report

EZH2 Inhibitor Well-Tolerated in Relapsed/Refractory Malignant Mesothelioma Patients

JUNE 04, 2018
Kristi Rosa
Researchers from Epizyme, a company dedicated to developing novel epigenetic therapies, have announced promising results from a phase 2 study assessing tazemetostat in relapsed/refractory malignant mesothelioma patients with BRCA1-associated protein 1 (BAP1) loss-of-function, at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

With about half (51%) of patients achieving control of their disease at 12 weeks, the study’s primary endpoint was met; in fact, the researchers report that the results surpassed the pre-specified disease control rate (DCR) threshold of ≥35%. They define DCR as patients having a complete response, a partial response (PR), or stable disease.

A total of 16 (26%) were reported to have maintained disease control for ≥24 weeks since beginning treatment with tazemetostat, an orally-administered, first-in-class, small molecule EZH2 inhibitor; two of the 16 patients achieved PR. Furthermore, all study participants were “heavily pretreated,” according to a recent press release, has had a median of 2 prior lines of therapy.

“Today’s findings show that tazemetostat monotherapy substantially delayed disease progression without significant toxicities, which is clinically meaningful,” Marjorie G. Zauderer, MD, commented in a recent statement. “This is encouraging for the patients and families impacted by mesothelioma, and for the oncologists who treat them.”

A form of cancer that develops in the thin layer of tissue that surrounds the lungs, chest wall, or abdomen, malignant mesothelioma is fairly rare in the United States, according to the American Cancer Society; only 3,000 new cases are diagnosed each year. The disease is thought to be caused by long-term exposure to asbestos and often presents as abdominal bloating and pain, chest pain, coughing, fatigue, shortness of breath, and weight loss in those who have it.

For the phase 2 multicenter, open-label study, researchers set out to assess 800 mg of tazemetostat monotherapy administered orally, two times per day, to adults with measurable relapsed/refractory malignant mesothelioma. A total of 74 patients were enrolled in the study which was split into 2 parts; the first focused on evaluating the safety and pharmacokinetics of the inhibitor and enrolled patients regardless of BAP1 status (n=13), while the second focused on determining DCR, and only enrolled patients with BAP1 loss-of-function (n=61). Overall response rate, progression-free survival, overall survival, safety, population PK, and response biomarkers were all included as secondary endpoints for the study.

The researchers found that tazemetostat was, overall, well-tolerated in participants; as such, no patients discontinued their regimen due to treatment-emergent adverse events (TEAE) and only 5 participants had TEAE-associated dose reductions. The TEAEs the were most common among participants included fatigue (32%), a decrease in appetite (28%), dyspnea (28%), nausea (27%), and cancer pain (26%).

“We’d like to thank the patients who participate in clinical trials and the caregivers who support them, in an effort to help advance the treatment of mesothelioma,” Epizyme’s president and chief executive officer Robert Bazemore, stressed in a recent statement. “We are encouraged by these positive results in this difficult-to-treat cancer, making it a compelling candidate for exploration as a combination therapy.”

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