According to results from the phase 2 NRG-GY014 trial, tazemetostat, a selective EZH2 inhibitor, failed to show single-agent efficacy among patients with recurrent/measurable endometrioid endometrial carcinoma or ovarian clear cell carcinoma not harboring ARID1A-mutations. However, potential was noted among patients with heavily-pretreated ovarian clear cell carcinoma with ARID1A mutations.

Alison Schram, MD, Memorial Sloan Kettering Cancer Center, New York, New York, presented these results at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancers in San Diego, California.

In stage 1 of this open-label trial, 62 heavily pre-treated patients with recurrent/measurable endometrioid endometrial carcinoma (n = 19), ovarian clear cell carcinoma (n = 10), or ARID1A-mutated ovarian clear cell carcinoma (n = 33) were enrolled to receive 800 mg of tazemetostat twice daily until disease progression or unacceptable toxicity. An additional 24 patients with pathogenic ARID1A-mutated ovarian clear cell carcinoma were enrolled and treated in stage 2. The primary end point was investigator-assessed overall response rate (ORR). Secondary end points included overall survival (OS), progression-free survival (PFS), and 6-month PFS. 

At analysis, the ORR of the endometrioid endometrial carcinoma cohort was 0% and the 6-month PFS rate was 25%. At that time, the cohort was closed to further accrual. In the ovarian clear cell carcinoma cohort, ORR was 11.1% which prompted activation of stage 2. Median PFS in the ARID1A-mutated ovarian clear cell carcinoma cohort was 3.7 months and OS was 14.8 months. The 6-month PFS rate in the pathogenic ARID1A-mutated ovarian clear cell carcinoma cohort was 24.2%. No new safety signals were identified. 

“Among patients with recurrent, pre-treated [endometrioid endometrial carcinoma and ovarian clear cell carcinoma], tazemetostat failed to show sufficient single-agent activity as defined by RECIST v1.1,” concluded Dr Scram et al. Despite this “within the heavily pre-treated ARID1Amut [ovarian clear cell carcinoma] cohort, a provocative 6-month PFS rate of 24.2% was noted.” 

Source: 

Schram A, Eskander RN, Sill MW, et al. Clinical activity of tazemetostat, an EZH2 inhibitor, in patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014). Presented at Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancers; March 16-18, 2024. San Diego, California.