Tazemetostat NDA Receives Priority Review in China for R/R Follicular Lymphoma

China’s National Medical Products Administration has accepted and granted priority review to a new drug application (NDA) for tazemetostat (Tazverik) for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL).¹

This NDA acceptance was supported by findings from a phase 2 multicenter, open-label bridging study (NCT05467943) conducted in China, as well as clinical trials conducted by Epizyme outside of China. The phase 2 trial enrolled 42 patients at least 18 years of age with histologically confirmed relapsed/refractory FL.^1,2 To be eligible for enrollment, patients needed to have at least 1 measurable lesion; a life expectancy of at least 12 weeks; an ECOG performance status of 0 to 2; and adequate bone marrow, renal, and hepatic function.² Patients were excluded if they had previously used tazemetostat or other EZH2 inhibitors; invasion of lymphoma to the central nervous system or pia mater; a history of bone marrow malignancies; or abnormalities associated with myeloproliferative neoplasms and myelodysplastic syndromes as observed by DNA sequencing and cytogenetic testing.

Overall response rate with tazemetostat in patients with relapsed/refractory FL harboring EZH2 mutations served as the study’s primary end point. Secondary end points included duration of response, progression-free survival, overall survival, safety, and pharmacokinetics in patients with relapsed/refractory FL regardless of EZH2 mutation status. All patients received 800 mg of tazemetostat twice daily in continuous 28-day cycles.

Findings from the phase 2 trial will be submitted for presentation at an upcoming medical meeting, according to a news release from HUTCHMED.¹

HUTCHMED is also leading the phase 1b/3 SYMPHONY-1 trial (NCT04224493) in China, which is evaluating the safety and efficacy of tazemetostat plus rituximab (Rituxan) and lenalidomide (Revlimid) vs placebo plus rituximab and lenalidomide in patients with relapsed/refractory FL who received 1 or more prior lines of therapy.

SYMPHONY-1 consists of 3 stages.³ Stage 1, now complete, was a safety run-in phase to investigate the safety of tazemetostat plus lenalidomide and rituximab and establish the recommended phase 3 dose of the combination for stage 2. Stage 2 is assessing the efficacy and safety of the combination in patients with FL with or without EZH2 mutations. In stage 2, patients with EZH2-mutant or –wild-type disease will be randomly assigned 1:1 to receive tazemetostat plus rituximab and lenalidomide or placebo plus rituximab and lenalidomide. Tazemetostat will be administered at 800 mg orally twice daily in continuous 28-day cycles. Rituximab will be administered at 375 mg/m² intravenously on days 1, 8, 15, and 22 of cycle 1, then on day 1 of cycles 2 to 5. Lenalidomide will be administered orally at 20 mg daily if patients have a creatinine clearance of at least 60 ml per minute or 10 mg daily if patients have a creatinine clearance of less than 60 ml per minute on days 1 to 21 for 12 cycles. The EZH2 wild-type population will undergo 1 futility interim analysis and 1 efficacy interim analysis. The EZH2-mutant population will undergo 1 efficacy interim analysis. Stage 3 is a long-term follow-up phase in which all patients will be followed for survival for 5 years after the last patient has been enrolled in the study.

In the United States, tazemetostat received FDA accelerated approval in June 2020 for the treatment of adult patients with relapsed/refractory EZH2-mutated FL who have received 2 or more prior systemic therapies, and adult patients with relapsed/refractory FL who have no satisfactory alternative treatment options.¹

The most common adverse effects observed with tazemetostat in patients with FL include upper respiratory tract infection, fatigue, nausea, abdominal pain, and musculoskeletal pain.

References

1. HUTCHMED announces NDA acceptance in China for tazemetostat for the treatment of relapsed or refractory follicular lymphoma with priority review status. News release. HUTCHMED. July 4, 2024. Accessed July 8, 2024. https://www.hutch-med.com/china-nda-acceptance-for-tazemetostat-for-follicular-lymphoma/
2. Tazemetostat for the treatment of relapsed/refractory follicular lymphoma. ClinicalTrials.gov. Updated September 30, 2022. Accessed July 8, 2024. https://clinicaltrials.gov/study/NCT05467943
3. A study to assess the efficacy, safety, pharmacodynamics, and pharmacokinetics of tazemetostat in combination with lenalidomide plus rituximab versus placebo in combination with lenalidomide plus rituximab in adult patients at least 18 years of age with relapsed/refractory follicular lymphoma. (SYMPHONY-1). ClinicalTrials.gov. Updated July 1, 2024. Accessed July 8, 2024. https://clinicaltrials.gov/study/NCT04224493