In a phase 2 study of patients with advanced epithelioid sarcoma, tazemetostat demonstrated durable clinical response and favorable safety, according to data being presented at the virtual 2020 ASCO Annual Meeting.

“More than 90% of epithelioid sarcoma tumors lack expression of INI1, an important component of epigenetic regulation. Loss of INI1 function allows another epigenetic modifier, EZH2, to become an oncogenic driver in tumor cells,” wrote Silvia Stacchiotti, MD, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and colleagues.

In the open-label, multi-center study, Dr Stacchiotti et al evaluated the efficacy of tazemetostat in patients with locally advanced or metastatic epithelioid sarcoma. They also sought to evaluate the objective response rate (ORR), disease control rate (DCR; ie, objective confirmed response of any duration or stable disease ≥32 weeks), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability.

A total of 62 patients with INI1-negative epithelioid sarcoma (median prior lines of therapy, 1) were enrolled in the study and given tazemetostat 800 mg twice daily as of September 2018.

Overall, 9 (15%) patients had confirmed partial responses, with an ORR and DCR of 15% and 26%, respectively. While DOR ranged from ≥7.1 weeks to ≥103.0 weeks, the median DOR was not reached.

In addition, the median OS was 82.4 weeks (95% CI, 47.4 to not estimable).

The study drug was found to be generally well tolerated.

The majority of treatment-emergent adverse events (TEAEs) were mild-to-moderate, with the most common (≥10%) regardless of attribution being fatigue (39%), nausea (35%), and cancer pain (32%).

Furthermore, there were 10 (16%) patients with treatment-related TEAEs grade ≥3, including anemia (6%) and decreased weight (3%).

No drug-related patient mortalities occurred, and the rate of discontinuation was low (1.7%).

“In the largest prospective clinical trial of epithelioid sarcoma to date, tazemetostat achieved disease control in 26% of patients with advanced epithelioid sarcoma who entered this study,” Dr Stacchiotti and colleagues wrote.

“Durable clinical response of the drug was documented. Tazemetostat demonstrated favorable safety with few patients with treatment-related AEs grade ≥3,” they concluded.—Hina M. Porcelli