FDA Approval Sought for Tazemetostat for Epithelioid Sarcoma

Shefali Agarwal, MD, MPH

A new drug application (NDA) has been submitted to the FDA for tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery, according to Epizyme, the manufacturer of the EZH2 inhibitor.

The NDA is based on data from the epithelioid sarcoma cohort of a phase II trial (NCT02601950) that will be presented at the 2019 ASCO Annual Meeting. Data published in an abstract released ahead of the meeting showed that among 62 patients with epithelioid sarcoma, the overall response rate was 15% (n = 9), comprised of all confirmed partial responses.

The disease control rate was 26% and the median duration of response was not reached (range, 7.1+ to 103+ weeks). The median overall survival among all 62 patients was 82.4 weeks (95% CI, 47.4 to not estimable).

“Epithelioid sarcoma is a rare and aggressive cancer that affects people in the prime of their lives, and we are very pleased to have recently submitted the NDA for tazemetostat for the treatment of people with this devastating cancer,” Shefali Agarwal, MD, MPH, chief medical officer of Epizyme, said in a press release.

“If approved, we believe tazemetostat has the potential to change the care of patients with this disease. We are incredibly grateful to the physicians and clinical teams who have helped advance tazemetostat to this stage, and, most notably, to the patients and caregivers who have participated in our clinical trials along the way. We look forward to continuing to engage with the FDA as we work to bring tazemetostat to patients and physicians in the United States,” added Agarwal.

At the data cutoff of September 17, 2018, the multicenter, open-label phase II trial enrolled 62 patients with locally advanced or metastatic epithelioid sarcoma whose tumors lacked INI expression. A lack of INI expression enables the epigenetic modifier EZH2 to act as an oncogenic driver in tumors cells. By targeting EZH2, Epizyme has the potential to block this process.

Patients had received a median of 1 (range, 0-9) prior line of therapy. Tazemetostat was administered at 800 mg twice daily.

The most common all-grade adverse events (AEs; ≥10%) were fatigue (39%), nausea (35%), and cancer pain (32%). Grade ≥3 treatment-emergent AEs (TEAEs) occurred in 16% (n = 10) of patients. Grade ≥3 TEAEs reported in at least 2 patients were anemia (6%) and decreased weight (3%). The rate of treatment discontinuation was 1.7%, and there were no deaths related to tazemetostat treatment.

“At Epizyme, our mission is to deliver new treatments for patients with cancer and other serious diseases, and today we stand one significant step closer to achieving that,” Robert Bazemore, president and chief executive officer of Epizyme, said in the press release.

“This submission is the culmination of years of hard work by our entire team, and I wish to congratulate them all on this accomplishment. Our epithelioid sarcoma program is strategically valuable to Epizyme and helps streamline our planned NDA submission in the fourth quarter, for patients with follicular lymphoma. Over the coming months, we have multiple anticipated clinical data and regulatory milestones, and we are well underway with commercialization readiness activities to support the potential launch of tazemetostat and our transition to a commercial-stage organization. 2019 is set to be a transformational year for Epizyme, and I am enthusiastic for our continued progress,” added Bazemore.

Stacchiotti S, Schoffski P, Jones R, et al. Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients (pts) with epithelioid sarcoma (ES) (NCT02601950). J Clin Oncol. 2019;37(suppl; abstr 11003).