NMPA conditionally approves tazerestat for the treatment of EZH2-mutant R/R follicular lymphoma

Tazemetostat has received conditional approval from the China National Medical Products Administration (NMPA) for the treatment of adult patients with relapsed or refractory EZH2-mutated follicular lymphoma (non-Hodgkin lymphoma) who have received 2 or more prior systemic therapies. This regulatory decision is supported by results from a multi-center, open-label, Phase 2 Bridging study (NCT05467943) conducted in China, as well as results from clinical trials conducted outside China.

This approval represents a significant advance in the management of this challenging disease. Most patients with [follicular lymphoma] experience multiple relapses throughout their lives, making treatment difficult and often leading to poor outcomes. Tazerestat has shown promising efficacy in clinical trials in patients carrying EZH2 mutations. The Chinese region is eager to make this transformational epigenetic therapy available to patients in China who have long sought new and effective treatment options.

This regulatory decision is the first nationwide regulatory approval for tazerestat in China, and the drug is the first and only EZH2 inhibitor approved by the National Medical Products Administration. The Bridging trial supporting the approval enrolled 42 patients at least 18 years of age with histologically confirmed relapsed/refractory follicular lymphoma with at least 1 measurable lesion; life expectancy of at least 12 weeks; ECOG performance status of 0 to 2; and normal bone marrow, renal and liver function. 2,3 Patients were excluded if they had previously been treated with tazolistatin or other EZH2 inhibitors; had lymphoma that invaded the central nervous system or leptomeninges; had a history of myeloid malignancy; or had abnormalities associated with myelodysplastic syndromes and myeloproliferative neoplasms.

Patients were stratified according to EZH2 mutation status (mutated vs. wild-type). All patients received 800 mg of tazerestat twice a day, with a cycle of 28 consecutive days. It is recommended that the interval between two doses is 12 hours. Overall response rate (ORR) in patients with relapsed/refractory EZH2-mutant follicular lymphoma was the trial's primary endpoint. Key secondary endpoints include overall survival (OS), safety and pharmacokinetics in patients with EZH2 wild-type relapsed/refractory follicular lymphoma.

Notably, in 2020, the U.S. Food and Drug Administration (FDA) approved tazerestat for the treatment of patients with EZH2-mutated relapsed/refractory follicular lymphoma who have received at least 2 prior lines of therapy, and those with relapsed/refractory follicular leukemia who have no other satisfactory treatment options.

The Confirmatory Phase 1b/3 SYMPHONY-1 trial (NCT04224493) is ongoing to verify the efficacy and safety of tazirestat in patients with relapsed/refractory follicular lymphoma who have received at least one prior treatment. The multicenter, international, double-blind, randomized, active-controlled, phase 3, biomarker-rich trial will assign patients to receive tazotatin or placebo, each in combination with rituximab and lenalidomide. The primary endpoint was to determine the recommended phase 2 doses of tazerestat plus lenalidomide and rituximab, and progression-free survival in the EZH2 mutant and wild-type populations. Secondary endpoints include pharmacokinetics, complete response (CR) rate, ORR, OS, duration of response, duration of CR, disease control rate, safety and quality of life.

References:https://www.onclive.com/view/nmpa-grants-conditional-approval-to-tazemetostat-for-ezh2-mutant-r-r-follicular-lymphoma