FDA Grants Priority Review to Tazemetostat for Epithelioid Sarcoma

The FDA has granted a priority review designation to a new drug application (NDA) 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.

UPDATE 1/23/2020: FDA Approves Tazemetostat for Epithelioid Sarcoma

The NDA is based on data from the epithelioid sarcoma cohort of a phase II trial (NCT02601950) that were presented at the 2019 ASCO Annual Meeting. Among 62 patients with epithelioid sarcoma, the overall response rate was 15% (n = 9), comprised of all confirmed partial responses.

At a median follow-up of 59.9 weeks, the median duration of response was not reached. The median overall survival (OS) among all 62 patients was 82.4 weeks (95% CI, 47.4 to not estimable). The median progression-free survival (PFS) was 23.7 weeks (95% CI, 14.7-25.7).

Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the NDA on or before January 23, 2020.

“We are thrilled with FDA’s acceptance of this first tazemetostat NDA submission for priority review, and to be an important step closer to achieving our mission of rewriting treatment for patients with cancer and other serious diseases,” Robert Bazemore, president and chief executive officer of Epizyme, said in a press release.

“This is a significant achievement in the development of this potentially first-in-class EZH2 inhibitor, and we look forward to working with FDA during the review. If approved, we believe tazemetostat could become an important new option in the treating physicians’ arsenal. We would like to extend our sincerest gratitude to those patients, families and medical teams who have participated in our clinical studies and helped bring tazemetostat to this stage,” added Bazemore.

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, tazemetostat has the potential to block this process.

The median patients age was 37 years, and there were 39 males and 23 females. Over 70% of patients had stage ≥III disease at diagnosis. The ECOG performance status was 0, 1, and 2, for 36, 21, and 5 patients, respectively. The cohort included 24 treatment-naïve patients and 38 patients who had received 1 to ≥3 prior lines of cancer treatment.

Tazemetostat was administered at 800 mg twice daily.

Among all 62 patients, 51% had a reduction in target lesion diameter. In the treatment-naïve group, there were 6 partial responses, 15 patients with stable disease, 2 patients with progressive disease, and 1 patient was not evaluable. Among previously treated patients, there were 3 partial responses, 20 patients with stable disease, 11 patients with progressive disease, and 4 patients were not evaluable.

The median PFS was 42.1 weeks in the treatment-naïve group compared with 14.7 weeks in the previously treated population. The median OS had not been reached in the treatment-naïve population and was 47.4 weeks in the previously treated group.

The most common all-grade treatment-related adverse events (AEs) were fatigue (27%), nausea (27%), decreased appetite (16%), vomiting (16%), diarrhea (13%), and anemia (10%). Grade ≥3 treatment-related AEs included 4 cases of anemia, 2 cases of decrease weight, and 1 case each of decreased appetite and fatigue.

There was 1 treatment discontinuation related to an AE, and there were no deaths related to tazemetostat treatment.

Epizyme is seeking an accelerated approval of tazemetostat. If the drug is approved under this designation, the company will need to show further supporting data through a confirmatory trial to receive full FDA approval of the treatment.

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).