(P 547) A PHASE II TRIAL OF TAZEMETOSTAT FOR PATIENTS WITH UNRESECTABLE OR METASTATIC EPITHELIOID SARCOMA (TAZETTA TRIAL)

Objective: Epithelioid sarcoma is an ultra-rare sarcoma that is recognized in less than 1% of patients with soft tissue sarcomas. Patients with surgically unresectable local recurrence or metastatic disease are treated with palliative chemotherapy, but the efficacy of chemotherapy is limited. Approximately 90% of patients with epithelioid sarcoma have SMARCB1/integrase interactor1(INI1) deficiency . The loss of INI1 function leads to overactivation of polycomb repressive complex 2 (PRC2). EZH2 is the catalytic subunit of PRC2, which regulates cell proliferation and is targeted by Tazemetostat, a potent and highly selective EZH2 inhibitor. The clinical efficacy of tazemetostat was evaluated by a multinational Phase 2 open-label basket study comprising 62 epithelioid sarcoma patients (NCT02601950). Tazemetostat has been reported to produce an overall response rate (ORR) of 15% with a median progression free survival (PFS) and overall survival (OS) of 5.5 months (95%CI:3.4-5.9) and 19 months (95% CI:11- not estimable) respectively. Here we present a phase 2 trial (TAZETTA trial; NCCH2107 trial) that will evaluate the efficacy and safety of tazemetostat in patients with advanced epithelioid sarcoma in Japan as a sub-study of the nationwide large registry project for rare cancers in Japan (MASTER KEY Project).

Methods: TAZETTA study is a non-randomized, single-arm, phase 2 study of tazemetostat in epithelioid sarcoma. Eligible patients with locally advanced or metastatic epithelioid sarcoma with loss of INI1 who have received previous treatment, including doxorubicin, an ECOG PS of 0 or 1 or 2, and ≥1 measurable lesion by RECIST v1.1. Tazemetostat will be administered 800 mg twice daily as a single oral agent in 28-day cycles. The primary endpoint is progression free survival rate at 18 weeks. The secondary endpoints include PFS, OS, ORR, disease control rate, duration of response and safety. Biomarker samples will also be collected for analysis.Ipsen provided a courtesy review of this presentation, the review was for scientific accuracy only, and no input on content was provided.

Results: Not Applicable

Conclusion: Not Applicable