Cao Junning, Chen Guangliang, Qiu Lihua, Zhang Liling, Jiang Ming, Cheng Ying, Zhang Qiaohua, Liu Lihong, Li Ping, Shuang Yuerong, Wang Huaqing, Xue Hongwei, Wu Huijing, Zheng Meifang, Zhou Keshu, Li Zhiming, Jing Hongmei, Yang Wei, Zhu Zunmin, Li Wenyu, Wangwu Jiaxuan, Huang Heyu, Jia Qiantao, Chen Dongmei, Fan Songhua, Shi M Ming, Su Weiguo
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Lymphoma, Tianjin Medical University Cancer Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Sino-US Center for Lymphoma Diagnosis and Treatment, Tianjin, China.
EClinicalMedicine. 2025 Aug 18;87:103399. doi: 10.1016/j.eclinm.2025.103399. eCollection 2025 Sep.
Tazemetostat, the first enhancer of zeste homolog 2 (EZH2) inhibitor approved by the U.S. Food and Drug Administration, has shown efficacy in a global population with relapsed or refractory (R/R) follicular lymphoma (FL). This phase 2 study was primarily designed as a registration-intent bridging trial of tazemetostat in Chinese patients with mutant ( ) R/R FL; the study also included evaluation in the wild-type ( ) population.
This multicentre, single-arm, phase 2 study was conducted at 19 sites in China. Eligible patients (aged ≥18 years) with histologically confirmed grade 1-3a FL were categorised by status: mutant ( , bridging cohort) and wild-type ( ), and received oral tazemetostat 800 mg twice daily in continuous 28-day cycles until investigator-assessed disease progression, intolerable toxicity, withdrawal of consent, or other protocol-specified criteria. The cohort primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Efficacy in the cohort was assessed in patients who received at least one dose of tazemetostat and had centrally confirmed FL. Efficacy in the cohort and safety in both cohorts were assessed in all patients who received at least one dose of tazemetostat. This study is registered with ClinicalTrials.gov, NCT05467943.
Between July 29, 2022, and Aug 31, 2023, 22 patients with R/R FL were enrolled (three lines [3L] of prior therapy, 31.8%; four lines [4L] of prior therapy or more, 27.3%). As of Aug 31, 2024 (median follow-up 14.4 months), IRC-assessed ORR was 63.6% (95% confidence interval [CI], 40.7%-82.8%), clinical benefit rate (CBR) was 90.9% (70.8%-98.9%), median duration of response (DoR) was not reached (18-month DoR rate, 51.6% [18.2%-77.3%]), and median progression-free survival was 15.4 (8.2-not estimable) months. All patients experienced treatment-related adverse events (TRAEs), and 13.6% had grade ≥3 TRAEs; most common TRAEs were haematological toxicities. For the cohort, 20 patients were enrolled (3L, 35.0%; ≥4L, 45.0%). Tazemetostat also demonstrated efficacy benefit and a manageable safety profile in the cohort, with an investigator-assessed ORR of 35.0% (95% CI, 15.4%-59.2%), CBR of 85.0% (62.1%-96.8%), and median DoR of 8.4 (1.9-15.7) months.
These results suggest that tazemetostat has a clinically meaningful efficacy and was well tolerated in Chinese patients with R/R FL. Larger trials are warranted. A multicentre, randomised, phase 3 trial of tazemetostat combined with lenalidomide plus rituximab vs. lenalidomide plus rituximab in patients with R/R FL is ongoing (NCT04224493).
HUTCHMED.
他泽司他是美国食品药品监督管理局批准的首个zeste同源物2（EZH2）抑制剂增强剂，已在全球复发或难治性（R/R）滤泡性淋巴瘤（FL）患者群体中显示出疗效。这项2期研究主要设计为他泽司他在中国携带突变（ ）R/R FL患者中的注册意向性桥接试验；该研究还包括对野生型（ ）群体的评估。
这项多中心、单臂、2期研究在中国的19个地点进行。符合条件的患者（年龄≥18岁）经组织学确诊为1-3a级FL，根据 状态分类：突变型（ ，桥接队列）和野生型（ ），并接受口服他泽司他800mg，每日两次，持续28天周期，直至研究者评估的疾病进展、无法耐受的毒性、撤回同意或其他方案规定的标准。 队列的主要终点是独立审查委员会（IRC）评估的客观缓解率（ORR）。在接受至少一剂他泽司他且经中心确认患有FL的患者中评估 队列的疗效。在所有接受至少一剂他泽司他的患者中评估 队列的疗效和两个队列的安全性。本研究已在ClinicalTrials.gov注册，NCT05467943。
在2022年7月29日至2023年8月31日期间，纳入了22例携带 突变的R/R FL患者（既往接受过三线[3L]治疗的占31.8%；既往接受过四线[4L]或更多线治疗的占27.3%）。截至2024年8月31日（中位随访14.4个月），IRC评估的ORR为63.6%（95%置信区间[CI]，40.7%-82.8%），临床获益率（CBR）为90.9%（70.8%-98.9%），中位缓解持续时间（DoR）未达到（18个月DoR率，51.6%[18.2%-77.3%]），中位无进展生存期为15.4（8.2-不可估计）个月。所有患者均经历了治疗相关不良事件（TRAEs），13.6%的患者发生≥3级TRAEs；最常见的TRAEs是血液学毒性。对于 队列，纳入了20例患者（3L，35.0%；≥4L，45.0%）。他泽司他在 队列中也显示出疗效获益和可控的安全性，研究者评估的ORR为35.0%（95%CI，15.4%-59.2%），CBR为85.0%（62.1%-96.8%），中位DoR为8.4（1.9-15.7）个月。
这些结果表明，他泽司他在携带R/R FL的中国患者中具有临床意义的疗效，且耐受性良好。有必要开展更大规模的试验。一项关于他泽司他联合来那度胺加利妥昔单抗对比来那度胺加利妥昔单抗治疗R/R FL患者的多中心、随机化3期试验正在进行中（NCT04224493）。
和黄医药。
