FDA Schedules ODAC Meeting on Tazemetostat for Epithelioid Sarcoma

The FDA has scheduled an Oncology Drugs Advisory Committee (ODAC) hearing for December 18, 2019, to discuss data supporting a new drug application (NDA) for tazemetostat as a treatment for patients with metastatic or locally advanced epithelioid sarcoma that is ineligible for curative surgery, according to Epizyme, the developer of the EZH2 inhibitor.

The application is primarily based on findings from a cohort of 62 patients with epithelioid sarcoma in an ongoing phase II study, which showed that the overall response rate was 15% (n = 9), comprised of all confirmed partial responses (PRs).

In July 2019, the FDA granted a priority review designation to the NDA for tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma that is not eligible for curative surgery. Under the Prescription Drug User Fee Act, the FDA is expected to make a decision on the approval by January 23, 2020.

In the multicenter, open-label phase II trial, investigators enrolled 62 patients with locally advanced or metastatic epithelioid sarcoma whose tumors lacked INI1 expression. A lack of INI1 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 age was 37 years; 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.

Results showed that, at a median follow-up of 59.9 weeks, 51% of the 62 patients 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 PRs, 20 patients with stable disease, 11 patients with progressive disease, and 4 patients were not evaluable.

Additionally, 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—not estimable). The median progression-free survival (PFS) was 23.7 weeks (95% CI, 14.7-25.7).

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.

Regarding safety, 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%). Additionally, 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 Announces FDA Advisory Committee Meeting to Review Tazemetostat for the Treatment of Patients with Epithelioid Sarcoma. Epizyme, Inc. Published December 2, 2019. https://bit.ly/2RbtgGp. Accessed December 3, 2019.