Efficacy and safety results of tazemetostat in Japanese patients with advanced epithelioid sarcoma: The phase 2 TAZETTA trial (NCCH2107).

11560 Background: Epithelioid sarcoma is an ultra-rare soft tissue sarcoma with limited treatment options. Tazemetostat, a selective EZH2 inhibitor, demonstrated antitumor activity in a global phase 2 study (NCT02601950) and has been approved for the treatment of epithelioid sarcoma in the US. We conducted a Japanese phase 2 study (TAZETTA; NCCH2107) as a sub-study within the framework of the nationwide rare cancer registry project in Japan (MASTER KEY Project) to evaluate the efficacy and safety of tazemetostat in patients with advanced epithelioid sarcoma. Methods: The TAZETTA study is a non-randomized, single-arm, phase 2 trial. Eligible patients had locally advanced or metastatic epithelioid sarcoma with loss of INI1, had received at least one prior chemotherapy including doxorubicin, had an ECOG performance status of 0–2, and at least one measurable lesion according to RECIST v1.1. Tazemetostat was administered orally at 800 mg twice daily in 28-day cycles. The primary endpoint was the progression-free survival (PFS) rate at 18 weeks by blinded independent central review. The threshold 18-week PFS rate was set at 5% and the expected rate at 30%. With a one-sided alpha of 0.05 and 80% power, the required sample size was 12 patients. To allow for ineligibility or non-treatment patients, 15 patients were planned. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR), disease control rate, duration of response, and safety. In the ancillary study, biomarker samples were collected and subjected to exploratory analysis. Results: Given the smooth patient accrual, 17 patients were enrolled between July 2023 and July 2024. The median age was 43 years; 13 patients were men and 4 were women. Proximal-type disease was observed in 11 patients (64.7%). The centrally assessed 18-week PFS rate was 31.3% (90% CI, 14.0–50.2), and the lower limit of the 90% CI met the predefined efficacy threshold. The median PFS was 2.9 months (95% CI, 1.6–5.6), and the median OS was 12.3 months (95% CI, 4.9–not estimable). Treatment-related adverse event with Grade ≥3 included lymphopenia (1pt, 5.9%). No treatment-related deaths were observed. Conclusions: Tazemetostat demonstrated clinically meaningful activity and a manageable safety profile in Japanese patients with advanced epithelioid sarcoma, consistent with the previous reports, supporting its role as a therapeutic option in this population. Clinical trial information: jRCT2031220523.