Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 422

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 422
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en’s SYMPHONY-1 (EZH-302) study, leading it in China.
Tazemetostat Mechanism of Action
EZH2 is one member of a class of histone methyltransferases (“HMTs”). It catalyzes the methylation of histone H3 at lysine 27 (H3K27) which controls expression of various genes and in turn plays a role in the normal physiology of many cell types. Dysregulation of EZH2 has been seen in a wide range of cancers and is associated with poor clinical prognosis and outcomes. Tazemetostat inhibits EZH2 which allows transcription of genes involved in functions such as cell cycle control and terminal differentiation and thus inhibits cancer cell proliferation.
Tazemetostat Clinical Development

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Treatment                                         Trial Name, Patient Focus                Sites        Phase             Status/Plan                                       NCT #      
Monotherapy                                   ​   r/r ≥3L EZH2m/EZH2w FL               ​   China    ​   II Bridging   ​   NDA accepted July 2024                        ​   NCT05467943
Tazemetostat+ lenalidomide + rituximab (R2)       SYMPHONY-1: r/r ≥2L EZH2m/EZH2w FL   ​   Global   ​   Ib/III        ​   Phase III ongoing Phase Ib data at ASH 2023       NCT04224493
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Phase II bridging study of tazemetostat in r/r ≥3L FL (NCT05467943)
In July 2022, we initiated a China Phase II open-label, two-cohort bridging study of tazemetostat in r/r ≥3L FL intended to support conditional registration in China. Patients received 800mg of tazemetostat BID. The primary objective is to evaluate ORR in patients with EZH2m (Cohort 1). The secondary objectives are to evaluate DoR, PFS and OS in patients with EZH2m and EZH2w (Cohort 2). Enrollment was completed with 42 patients in September 2023. In July 2024, NDA was accepted by NMPA with