The FDA granted accelerated approval of tazemetostat (Tazverik) based on data reported in a phase II clinical trial of the methyltransferase inhibitor.
The FDA has granted accelerated approval of tazemetostat (Tazverik) for the treatment of adults and pediatric patients aged 16 and older with metastatic or locally advanced epithelioid sarcoma (ES) not eligible for complete resection, according to Epizyme, the agent’s developer.
The approval was based on overall response rate (ORR) and duration of response in a phase II clinical trial of the methyltransferase inhibitor.
“Despite industry advancements, there are limited therapeutic options for treating patients with epithelioid sarcoma who struggle with high rates of recurrence and toxicities associated with currently used therapies,” study investigator Gary K. Schwartz, MD, chief of hematology and oncology at Columbia University and NewYork-Presbyterian Hospital, deputy director of the Herbert Irving Comprehensive Cancer Center, and professor of oncology at Columbia University Vagelos College of Physicians and Surgeons, said in a press release. “The Tazverik data from the ES cohort in Epizyme’s phase II trial support its potential to provide clinically meaningful and durable responses, and tolerability for ES patients. This approval of Tazverik represents an important advancement in the treatment of patients with ES.”
In this multi-center study of 62 patients with histologically confirmed, metastatic or locally advanced ES, patients received 800 mg of tazemetostat orally twice daily until disease progression or unacceptable toxicity. Tumor response assessments were performed every 8 weeks.
The ORR (95% CI) was 15% (7%, 26%), with 1.6% of the patients achieving a complete response and 13% achieving a partial response. Of the responders in the trial, 67% had a duration of response of 6 months or longer.
The most common adverse reactions (≥20%) were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Serious adverse reactions developed in 37% of patients, and one patient permanently discontinued tazemetostat because of an adverse reaction of altered mood. Serious adverse reactions in ≥3% of patients who received the inhibitor were hemorrhage, pleural effusion, skin infection dyspnea, pain, and respiratory distress.
Dosage interruptions caused by an adverse reaction occurred in 34% of patients who were treated with tazemetostat, and the most common adverse reactions requiring dosage interruptions in ≥3% were hemorrhage, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST).
Dose reduction as a result of an adverse reaction only took place in one patient who received the inhibitor, and the dose was reduced due to a decreased appetite in the patient.
“For people with epithelioid sarcoma, an aggressive life-threatening cancer that affects young adults, having new treatment options can offer much needed hope,” Denise Reinke, MS, NP, NBA, president and chief executive officer of the Sarcoma Alliance for Research through Collaboration (SARC) and co-founder of the Sarcoma Coalition, said in a press release.
Continued approval for this indication is dependent upon verification and description of the clinical benefit in a confirmatory trial. Epizyme indicated that it is continuing to expand enrollment in cohort 6 of the phase II study, which has currently enrolled 44 patients, for a total of at least 60 patients with epithelioid sarcoma. The expansion is supposed to provide more patient experience for possible future inclusion in the label.
Additionally, the company will be conducting certain post-marketing activities, such as clinical pharmacology evaluations to determine the effect of tazemetostat on liver function and the effect of CYP3A inhibitors and inducers on the inhibitor to inform aspects of the prescribing information. The company’s ongoing, global, randomized, controlled confirmatory trial evaluating the combination of tazemetostat plus doxorubicin (Adriamycin) compared with doxorubicin plus placebo as a front-line treatment for ES is also underway.
Epizyme Announces U.S. FDA Accelerated Approval of TAZVERIK (tazemetostat) for the Treatment of Patients with Epithelioid Sarcoma [news release]. Cambridge, Massachusetts. Published January 23, 2020. businesswire.com/news/home/20200123005858/en/Epizyme-Announces-U.S.-FDA-Accelerated-Approval-TAZVERIK™. Accessed January 24, 2020.