Tazemetostat Demonstrates Effiacy, Safety Among Patients With EZH2-Mutant and EZH2 Wild-Type Relapsed/Refractory Follicular Lymphoma

Tazemetostat, an oral EZH2 inhibitor, demonstrated efficacy and safety among Chinese patients with EZH2-mutant (EZH2^mut) or EZH2 wild-type (EZH2^wt) relapsed/refractory (R/R) follicular lymphoma (FL), according to study results published in eClinicalMedicine. 

Following the US FDA approval of tazemetostat, this study was “primarily designed as a registration-intent bridging trial of tazemetostat in Chinese patients with EZH2-mutant R/R FL,” the study authors noted.

Researchers conducted a multicenter, open-label, phase 2 study and enrolled 42 patients with histologically confirmed grade 1 to 3a FL across 19 sites in China. Patients received tazemetostat 800 mg twice daily in continuous 28-day cycles until disease progression or intolerable toxicity. 

The primary endpoint in the EZH2^mut cohort was objective response rate (ORR) defined as the proportion of patients with best overall response (BOR) of complete response (CR) or patiral second (PR). Secondary end points included CR rate, clinical benefit rate (CBR), duration of response (DoR), CBR, time-to-response (TTR), and progression-free survival (PFS), and overall survival (OS). 

Among the EZH2^mut cohort, 22 patients with EZH2^mut FL were included and the median age of all patients was 53.5 (range, 35 to 72) years. In the EZH2^wt  cohort, 20 patients were included, and the median age of all patients was 57.5 (range, 36 to 76) years. The median lines of prior therapy for both cohorts was 3 (range, 2 to 7). 

At a median follow up of 14.4 months, the ORR for the EZH2^mut was 63.6% (95% confidence interval [CI], 40.7 to 82.8). The CR rate was 18.2% and a PR of 45.5%. The CBR was 90.9% (95% CI, 70.8 to 98.9). The median DoR was not reached, at 18 months the DoR rate was 51.6% (95% CI, 18.2 to 77.3). The median PFS was 15.4 months (95% CI, 8.2 to not evaluable). Additionally, the TTR was 3.7 (range, 1.7 to 8.2) months. At 18 months the OS was 87.5% (95% CI, 38.7 to 98.1). 

In the EZH2^wt cohort at the median follow-up was 21.4 months, tazemetostat also demonstrated clinical activity, with an investigator-assessed ORR of 35.0% (95% CI, 15.4 to 59.2). A CR was not reached by any patient in this group CBR of 85.0% (95% CI, 62.1–96.8), however, 35.0% of patients achieved a PR. The CBR was 85.0% (95% CI, 62.1 to 96.8). The median DoR was 8.4 (95% CI, 1.9 to 15.7) months. Additionally, the median PFS was 8.2 (95% CI, 3.7 to 13.8) months and the median OS was not reached.

In terms of safety, the most common treatment-emergent adverse events among patients in the EZH2^mut cohort were platelet count decrease (36.4%), white blood cell count decrease (31.8%), anemia (27.3%), and hypertriglyceridaemia (27.3%). 

The researchers concluded, “the results of this phase 2 study suggest that tazemetostat has a clinically meaningful efficacy and favorable safety profile in patients with relapsed or refractory FL.”

Source:

Cao J, Chen G, Qiu L, et al. Efficacy and safety of tazemetostat, an EZH2 inhibitor, in Chinese patients with relapsed/refractory follicular lymphoma: a multicentre, single-arm, phase 2 study. EClinicalMedicine. August 18, 2025. doi:10.1016/j.eclinm.2025.103399