A Phase 2, Open-label, Single-Arm Clinical Trial to Investigate the Efficacy and Safety of Oral Tazemetostat for the Treatment of Adult Participants Age 18 and Over With Relapsed/Refractory Follicular Lymphoma Lacking the EZH2 Gain-of-Function (GOF) Mutation

The purpose of this research study is to learn about the effectiveness and safety of the study drug, tazemetostat, in adults with relapsed/refractory follicular lymphoma whose tumours do not have an "EZH2 gain-of-function" genetic mutation. Follicular lymphoma is a blood cancer. It affects white blood cells called lymphocytes. White blood cells normally help to fight infections, but when you have follicular lymphoma, the blood cells can form tumours in your body. 'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2" mutation who have no satisfactory alternative treatment options.
This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2 gain-of-function" genetic mutation and who previously received therapies commonly used in the U.S. in your body.
'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2 gain-of-function" mutation who have no satisfactory alternative treatment options. This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2" genetic mutation and who previously received therapies commonly used in the U.S.
In this study, all participants will receive the study drug. It will be taken by mouth (orally), as a tablet, twice daily. The sizes and number of tumours according to scan results will be collected as well as results of safety tests (such as physical examinations and laboratory tests).
The study consists of 4 periods:
* Screening period may take up to 4 weeks and require at least 1 visit.
* Treatment period will require 2 visits for each of the first 2 months, followed by 1 visit every month for the remainder of the first 12 months, followed by 1 visit every 3 months (except for women of childbearing potential [WOCBP], who will continue to have a pregnancy testing every month) until unacceptable toxicity, disease progression, or the start of new systemic anticancer therapy, whichever is first.
* Safety follow-up period will last for 1 month after the last dose of tazemetostat, and it will end with 1 visit or telephone call.
* Long-term follow-up period is only for participants who stop taking tazemetostat while their disease continues to respond; this period will last until disease progression, start of new cancer treatment, or death from any cause, whichever is first, and will require a visit every 3 months.
Tazemetostat will be provided to participants who tolerate it for as long as their disease does not progress.
Participants may be transferred to another study or program after about 2 years for continued treatment with tazemetostat or for long-term follow-up. Patients may withdraw consent to participate at any time.

开始日期2025-09-02

申办/合作机构

Epizyme, Inc.

[+1]

NCT06824701

/ Not yet recruiting临床1期IIT

A Phase 1b Study of Tazemetostat in Combination With Zanubrutinib and Anti-CD20 Monoclonal Antibody in Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphomas

The purpose of this clinical trial is to learn if the study drug Tazemetostat combined with Zanubrutinib and anti-CD20 monoclonal antibody is safe and effective in treating patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

开始日期2025-06-01

申办/合作机构

University of Utah

[+1]

NCT06575686

/ Recruiting临床2期IIT

A Phase 2 Study of Epcoritamab Plus Tazemetostat for Treatment of Relapsed/Refractory Follicular Lymphoma

This phase II trial tests the safety, side effects and effectiveness of epcoritamab and tazemetostat in treating patients with grade I-IIIa follicular lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab is a bispecific monoclonal antibody that binds to two different antigens on the surface of cancer cells that may help the body's immune system attack the cancer and may interfere with the ability of the cancer cells to grow and spread. Tazemetostat, a EZH2 inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving epcoritamab and tazemetostat may be safe, tolerable and/or effective in treating patients with relapsed or refractory grade I-IIIa follicular lymphoma.

开始日期2025-04-20

申办/合作机构

City of Hope National Medical Center

[+1]

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100 项与氢溴酸他泽司他相关的专利（医药）

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455

项与氢溴酸他泽司他相关的文献（医药）

2025-12-01·FUNCTIONAL & INTEGRATIVE GENOMICS

Polycomb repressive complex 2 (PRC2) pathway’s role in cancer cell plasticity and drug resistance

Review

作者: Tabari, Mohammad Amin Khazeei ; Khan, Haroon ; Javan, Alireza ; Larsen, Danaé S ; Rezaee, Aryan ; Heidari, Mohammad Mahdi ; Sanaye, Pantea Majma ; Hadipour, Mahboube ; Goleij, Pouya ; Daglia, Maria

Polycomb Repressive Complex 2 (PRC2) is a central regulator of gene expression via the trimethylation of histone H3 on lysine 27. This epigenetic modification plays a crucial role in maintaining cell identity and controlling differentiation, while its dysregulation is closely linked to cancer progression. PRC2 silences tumor suppressor genes, promoting cell proliferation, metastasis, epithelial-mesenchymal transition, and cancer stem cell plasticity. Enhancement of zeste homolog 2 (EZH2) overexpression or gain-of-function mutations have been observed in several cancers, including lymphoma, breast, and prostate cancers, driving aggressive tumor behavior and drug resistance. In addition to EZH2, other PRC2 components, such as embryonic ectoderm development (EED) and suppressor of zeste 12, are essential for complex stability and function. EED, in particular, enhances EZH2 activity and has emerged as a therapeutic target. Inhibitors like MAK683 and EED226 disrupt EED's ability to maintain PRC2 activity, thereby reducing H3K27me3 levels and reactivating tumor suppressor genes. Valemetostat, a dual inhibitor of both EZH2 and EED, has shown promising results in aggressive cancers like diffuse large B-cell lymphoma and small-cell lung cancer, underlining the therapeutic potential of targeting multiple PRC2 components. PRC2's role extends beyond gene repression, as it contributes to metabolic reprogramming in tumors, regulating glycolysis and lipid synthesis to fuel cancer growth. Furthermore, PRC2 is implicated in chemoresistance, particularly by modulating DNA damage response and immune evasion. Tazemetostat, a selective EZH2 inhibitor, has demonstrated significant clinical efficacy in EZH2-mutant cancers, such as non-Hodgkin lymphomas and epithelioid sarcoma. However, the compensatory function of enhancer of zeste homolog 1 (EZH1) in some cancers requires dual inhibition strategies, as seen with agents like UNC1999 and Tulmimetostat, which target both EZH1 and EZH2. Given PRC2's multifaceted role in cancer biology, its inhibition represents a promising avenue for therapeutic intervention. The continued development of PRC2 inhibitors and exploration of their use in combination with standard chemotherapy or immunotherapy has great potential for improving patient outcomes in cancers driven by PRC2 dysregulation.

2025-08-01·BRAIN BEHAVIOR AND IMMUNITY

EZH2-mediated suppression of TIMP1 in spinal GABAergic interneurons drives microglial activation via MMP-9-TLR2/4-NLRP3 signaling in neuropathic pain

Article

作者: Pan, Yinbing ; Wu, Xuefeng ; Wu, Xudong ; Liu, Wentao ; Hu, Fan ; Guo, Haiyue ; Yang, Shuo ; Jiang, Chun-Yi ; Wan, Li

Effective management of neuropathic pain remains a significant challenge due to the limited understanding of its underlying mechanisms. We found that the FDA-approved enhancer of zeste homolog 2 (EZH2) inhibitor, EPZ6438, can prevent the development of neuropathic pain caused by chronic constriction injury (CCI). Therefore, we utilized EPZ6438 as a probe to investigate the molecular events involved in the early stage of neuropathic pain. RNA-seq analysis reveals that EPZ6438 significantly upregulates Timp1 transcription in the spinal cord of mice. As a specific endogenous inhibitor of MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP1) levels significantly decrease in the cerebrospinal fluid of both neuropathic pain patients and the CCI rat models. Importantly, intrathecal administration of mouse recombinant TIMP1 protein (rmTIMP1) reverses CCI-induced mechanical and thermal hyperalgesia. Mechanistically, substance P released from primary sensory neurons suppresses TIMP1 in spinal GABAergic interneurons by elevating EZH2 expression, which enhances H3K27me3 enrichment at the Timp1 promoter. Blocking spinal NK1R effectively prevents the downregulation of TIMP1 and alleviates CCI-induced hyperalgesia. The imbalance between TIMP1 and MMP-9 leads to NLRP3 activation in spinal microglia and increases IL-1β maturation via TLR2/4 pathway. TIMP1 injection eliminates MMP-9-induced NLRP3 activation and blocks hyperalgesia, suggesting that TIMP1 is a critical gatekeeper in preventing neuroinflammation during neuropathic pain development.

2025-04-01·EClinicalMedicine

Efficacy of tazemetostat in combination with R-CHOP in elderly patients newly diagnosed with diffuse large B cell lymphoma: results of the EpiRCHOP phase II study of the LYSA

Article

作者: Guidez, Stéphanie ; Crochet, Gilles ; Bonnet, Christophe ; Gastinne, Thomas ; Houot, Roch ; Ysebaert, Loic ; Morschhauser, Franck ; Molina, Thierry Jo ; Bachy, Emmanuel ; Jardin, Fabrice ; Thieblemont, Catherine ; Veresezan, Liana ; Sarkozy, Clémentine ; Dubois, Sydney ; Herbaux, Charles ; Ruminy, Philippe ; Haioun, Corinne ; Bohers, Elodie ; Pica, Gian Matteo ; Portugues, Cédric ; Ribrag, Vincent ; Choquet, Sylvain

Background:

In the phase I Epi-RCHOP study (NCT02889523), we reported that R-CHOP-tazemetostat was well tolerated with the recommended phase II dose, consistent with monotherapy.

Methods:

Phase II included newly diagnosed diffuse large B cell lymphoma patients aged 60-80 years who received six cycles of rituximab-CHOP (R-CHOP) with continuous tazemetostat (800 mg BID), plus two cycles of tazemetostat and rituximab (cycles 7 and 8), from July 31, 2020 to July 18, 2022. Primary endpoint was positron emission tomography complete metabolic response (CMR). Sample size was calculated with H0 of 70% and H1 assumption of 80%.

Findings:

The trial enrolled 122 patients: median age 70 (60-80), 90.2% with stage III-IV, and 73.8% with International Prognostic Index 3-5. Overall, 100 patients (82%) received eight cycles, while 22 had premature treatment discontinuation (PTD), including 12 during the first two cycles. Reasons for PTD were consent withdrawal (N = 10), adverse events (N = 6), death (N = 2), protocol deviation (N = 2), progressive disease (N = 1), and physician decision (N = 1). The median percentage of relative dose intensity of tazemetostat and R-CHOP exceeded 90%, but required a protocol amendment and reduction in vincristine dosage at 1 mg full dose. At the end of treatment or PTD, 92/122 patients (75.4%) achieved CMR, eight (6.6%) partial metabolic response, five (4.1%) progressive disease, two (1.6%) died (septic shock), and 15 (12.3%) were not evaluated. Sensitivity analysis, excluding ten non-evaluated patients who withdrew consent, showed CMR in 82.1%. After a median follow-up of 18.5 months (IQR: 15.4-21), estimated progression-free and overall survival at 18 months were 77.7% (95% CI: 67.5-85.1%) and 88.8% (95% CI: 79.9-93.9%), respectively.

Interpretation:

R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. Complementary biomarker studies are needed for a more personalized approach.

Funding:

This study was sponsored under a grant from Ipsen.

170

项与氢溴酸他泽司他相关的新闻（医药）

2025-04-30

·医药速览

Science子刊：抑制DNMT1，给T细胞（CAR-T）增加NK细胞功能，显著增强抗肿瘤活性

T细胞和NK细胞杀伤肿瘤功能不相同，如果把NK细胞的功能添加到T细胞上，或者CART细胞上，能不能让T杀伤癌细胞能力增强呢？3月21日，《Science Immunology》一篇标题为：DNMT1 inhibition reprograms T cells to NK-like cells with potent antitumor activity 的文章，研究了DNMT1（DNA甲基转移酶1）在维持T细胞特性和抑制其向自然杀伤(NK)样细胞转变中的关键作用。通过抑制DNMT1，研究人员成功将T细胞（包括CAR-T细胞）重编程为具有增强抗肿瘤活性的NK样细胞，体外体内杀伤肿瘤能力显著增强。此前研究表明，转录因子BCL11B的失活可以将T细胞重编程为诱导型T到NK细胞（ITNKs），展现出抗肿瘤活性。然而，BCL11B是如何抑制自然杀伤（NK）细胞转录程序的分子机制尚不清楚。蛋白质组学分析发现，BCL11B在T细胞中与DNMT1和UHRF1形成复合物，共同维持DNA甲基化状态。这一表观遗传机制对抑制NK细胞相关基因的表达至关重要。敲除DNMT1或UHRF1会导致T细胞中NK细胞标志物NKp30和NKp46的显著上调，表明UHRF1-DNMT1轴在维持T细胞特性方面的重要作用。使用非核苷类DNMT1选择性抑制剂GSK3484862（GSK862）处理CD4和CD8 T细胞后，这些细胞表现出NK细胞特征，包括NKp30和NKp46的表达上调。类似地，FDA批准的泛DNMT抑制剂地西他滨（DAC）也能在原代人T细胞中诱导NK细胞标志物的表达。这些结果表明，通过化学手段干预DNMT1/UHRF1轴，可以有效模拟BCL11B缺失的效应，为T细胞重编程提供了一种高效且可控的策略。敲除DNMT1或UHRF1以及使用GSK862处理的T细胞在UMAP空间中形成独特的细胞簇，这些细胞表现出NK细胞标志物（如NKp30、NKp46）的上调和T细胞特异性转录因子TCF7的下调，同时还显著增加了杀伤细胞免疫球蛋白样受体（KIRs）家族成员（如KIR3DL1、KIR2DL2/L3/S2、KIR2DS1）和NKp44的表达。此外，DNMT1抑制上调了CD94和NKG2A，但未诱导NK细胞激活受体NKG2C或ADCC相关受体CD16的表达。部分NK细胞相关基因（如SIGLEC7、TYROBP、KIR家族成员）在DNMT1/UHRF1抑制组中显著上调，而在BCL11B缺失组中无明显变化，而另一些基因（如IL18R1、NCAM1、ZNF683）则更倾向于在BCL11B缺失时上调。这些数据表明，抑制维持性DNA甲基化和敲除BCL11B虽然都能诱导T细胞向NK样细胞转化，但两者调控的基因网络存在显著差异，展现了共享和独特的转录特征。抑制DNMT1生成的NK样细胞展现出比BCL11B缺失ITNKs更强的细胞毒性，可能归因于其分泌更高水平的干扰素-γ（IFN-γ）、颗粒酶A/B、颗粒溶素和穿孔素。抗体阻断实验进一步证实，NKp30和NKp46在NK样细胞对K562细胞的杀伤中起关键作用。这些NK样细胞能够通过NCRs和TCRs识别多种癌细胞系，例如有效裂解表达OKT3的NALM6细胞，而对野生型NALM6无显著作用。这表明，DNMT1抑制重编程的NK样细胞兼具天然免疫和适应性免疫的双重识别能力。NK样细胞在体内展现优异抗肿瘤活性，并可通过CAR工程化增强特异性。在免疫缺陷NSI小鼠模型中评估了NK样细胞对HepG2和K562异种移植瘤的抗肿瘤效果。结果显示，与BCL11B缺失ITNKs相比，由DNMT1抑制或GSK862处理生成的NK样细胞在两种模型中均更显著地抑制肿瘤生长并延长小鼠生存期。肿瘤浸润的NK样细胞高表达活化标志物CD69，而PD1和LAG3的表达水平低于对照组。体外扩增和再刺激后，这些细胞分泌更高水平的颗粒酶B和颗粒溶素。为提高肿瘤识别特异性，研究将抗CD19或抗间皮素（MSLN）CAR转导入GSK862处理的NK样细胞中，结果表明这些CAR-NK样细胞在体内外均展现出优于传统CAR-T细胞的抗肿瘤活性。这些数据证明，DNMT1抑制重编程的NK样细胞不仅具备强效抗肿瘤能力，还可通过CAR工程化实现靶向治疗，进一步增强其临床应用潜力。DNMT1的非酶功能通过稳定BCL11B抑制T细胞向NK样细胞重编程。研究发现，DNMT1与BCL11B相互作用，并通过其非酶功能维持BCL11B的蛋白稳定性，从而支持T细胞特性。DNMT1-BCL11B相互作用在抑制T细胞向NK样细胞重编程中的关键作用。GSK862处理显著上调CD4和CD8 T细胞中NKp30和NKp46的表达，但外源性过表达BCL11B能够部分逆转这一效应。这表明，DNMT1通过与BCL11B的物理相互作用维持其稳定性，从而抑制T细胞向NK样细胞的转化。进一步发现，抑制DNMT1和EZH2可协同重编程T细胞，增强NK样细胞的生成和抗肿瘤活性。DNA甲基化和H3K27me3共同抑制NK细胞相关基因的表达，而联合使用DNMT1抑制剂（如GSK862）和EZH2抑制剂（如EPZ6438）可显著解除这种抑制，促进NK细胞特异性基因的表达和染色质开放性。这种协同作用通过激活NK细胞相关信号通路（如细胞毒性因子和免疫调控基因）实现，从而提升T细胞向NK样细胞的转化效率及其抗肿瘤功能。这些结果表明，DNA甲基化和H3K27me3是防止T细胞转变为NK样细胞的双重保障机制。最后，这项研究揭示了DNMT1在维持T细胞特性和抑制NK细胞程序中的关键分子机制，并提出了通过使用表观遗传抑制剂（特别是DNMT1抑制剂，以及与EZH2抑制剂联合使用）将T细胞转化为具有增强抗肿瘤活性的NK样细胞的新策略，为癌症免疫治疗提供了新的思路和潜在的细胞来源。参考资料：Yao Li et al. ,DNMT1 inhibition reprograms T cells to NK-like cells with potent antitumor activity.Sci. Immunol.10,eadm8251(2025).DOI:10.1126/sciimmunol.adm8251推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yong_wang@pku.edu.cn获取更多信息。©2021 医药速览保留所有权利往期链接“小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记PROTAC技术| 抗体药物| 抗体药物偶联-ADC核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

细胞疗法免疫疗法临床研究

2025-04-28

·GlobeNewswire-Health Care

Arvinas Shares New Preclinical Combination Data for the PROTAC BCL6 Degrader, ARV-393, at the 2025 American Association for Cancer Research Annual Meeting

– ARV-393 demonstrated strong synergistic antitumor activity, including complete regressions, in combination with standard-of-care chemotherapy, biologics, and select investigational oral small molecule inhibitors – – Findings support continued evaluation of ARV-393 combinations in non-Hodgkin lymphoma – NEW HAVEN, Conn., April 28, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, today presented data from preclinical combination studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader. BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. Data demonstrated synergistic antitumor activity, including complete regressions, in combination with standard of care (SOC) chemotherapy, SOC biologics, and investigational oral small molecule inhibitors (SMIs) in high grade B-cell lymphoma (HGBCL) and aggressive diffuse large B-cell lymphoma (DLBCL) models. The results from these preclinical studies were shared in a poster presentation at the 2025 American Association for Cancer Research (AACR) annual meeting in Chicago, Illinois. Key findings from the studies included: ARV-393 in combination with SOC chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), induced significantly greater tumor growth inhibition compared with rituximab, CHOP, R-CHOP, or ARV-393 alone, with complete tumor regressions in all mice treated with the ARV-393 and R-CHOP combination.ARV-393 in combination with SOC biologics targeting CD20 (rituximab), CD19 (tafasitamab), or CD79b (polatuzumab vedotin) resulted in tumor regressions and demonstrated significantly stronger tumor growth inhibition compared with each agent alone.In preclinical models, ARV-393 increased CD20 expression, providing additional support for the exploration of combinations with CD20-targeted agents and in the context of low or loss of CD20 expression.ARV-393 in combination with investigational small molecule inhibitors targeting clinically validated oncogenic drivers of lymphoma, such as BTK (acalabrutinib), BCL2 (venetoclax), or EZH2 (tazemetostat), resulted in superior tumor growth inhibition compared with each agent alone, with tumor regressions in all mice treated with the combinations. “Given that combination regimens are the foundation of lymphoma treatment, we are encouraged by the strength of these preclinical combination data, which demonstrate complete tumor regressions in aggressive lymphoma models,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “We believe these preclinical data demonstrate potential for broad combinability of ARV-393 and provide a compelling rationale for considering combination strategies as we work to bring forward new therapeutic options for lymphoma patients.” A Phase 1 study of ARV-393 is enrolling patients with relapsed/refractory non-Hodgkin lymphoma, including DLBCL (NCT06393738). Additional detail on the ARV-393 data presentation at AACR 2025: Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, Combined With Biologics or Small-Molecule Inhibitors Induces Tumor Regressions in Diffuse Large B-Cell Lymphoma ModelsAbstract: 1655Session Title: Degraders and Glues 2 Session Type: Experimental and Molecular TherapeuticLocation: Poster Section 18Poster Board Number: 15Date: Monday, April 28, 2025Lecture Time: 9:00 a.m. – 12:00 p.m. CT About ARV-393ARV-393 is an investigational, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. During B-cell development, tightly controlled BCL6 protein expression regulates >600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation, and genomic instability. PROTAC-mediated degradation has the potential to address the historically undruggable nature of BCL6. ARV-393 is currently in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma. About ArvinasArvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROteolysis TArgeting Chimera (PROTAC) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential for Arvinas’ investigational oral PROteolysis TArgeting Chimera (PROTAC) degrader ARV-393 to treat relapsed/refractory non-Hodgkin lymphoma; the preclinical data for ARV-393 demonstrating the potential for broad combinability and supporting continued evaluation of ARV-393 combinations in non-Hodgkin lymphoma associated with B-cell lymphoma 6 protein (“BCL6”) dysfunction; and PROTAC-mediated degradation having the potential to address the historically undruggable nature of BCL6.. All statements, other than statements of historical facts, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: whether Arvinas will be able to successfully conduct and complete development for its product candidates, including ARV-393, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials on its expected timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2024 and subsequent other reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. Contacts:Investors:Jeff Boyle+1 (347) 247-5089Jeff.Boyle@arvinas.com Media:Kirsten Owens+1 (203) 584-0307Kirsten.Owens@arvinas.com

临床1期AACR会议蛋白降解靶向嵌合体

2025-04-09

·生物制品圈

2025 医药监管动态：多款新药获批，市场格局迎新变

2025 年上半年，全球医药监管领域动态频出，众多药企的产品在审批进程中取得关键进展。这些监管决策不仅关乎药企的发展，也为患者带来了新的希望，同时推动着全球医药市场格局的重塑。肿瘤药物：多款新药获批，治疗格局改写肿瘤治疗领域一直是医药创新的前沿阵地，2025 年也不例外。阿斯利康和第一三共的 Enhertu 在欧洲获批用于治疗 HR 阳性、HER2 低表达或超低表达的乳腺癌患者，成为这一特定患者群体的首款 HER2 靶向疗法。基于 DESTINY - Breast06 试验结果，Enhertu 展现出显著优势，相比化疗，它能降低 38% 的疾病进展或死亡风险。这一批准为乳腺癌治疗开辟了新路径，为那些对内分泌治疗不再敏感的患者带来了新的生存希望。阿斯利康的 Imfinzi 也在肺癌治疗方面取得新进展，在欧洲获批用于可切除的非小细胞肺癌（NSCLC）高复发风险患者的围手术期治疗方案。依据 AEGEAN 试验结果，Imfinzi 联合化疗能使疾病复发、进展或死亡风险降低 32%。这一成果对于改善肺癌患者预后意义重大，有望提高患者的生存率和生活质量。此外，Epizyme 的淋巴瘤药物 Tazverik 在中国获得有条件批准，成为中国首个获批的 EZH2 抑制剂，开启了 Hutchmed 在血液恶性肿瘤领域的征程。而 Bristol Myers Squibb 的 Breyanzi 在欧洲获批用于治疗复发或难治性滤泡性淋巴瘤，其基于全球 2 期研究 TRANSCEND FL 的出色数据，患者缓解率高达 97.1%，完全缓解率达 94.2%。这些新药的获批，为肿瘤患者提供了更多治疗选择，推动肿瘤治疗向精准化、个性化迈进。罕见病药物：突破困境，带来新曙光罕见病患者群体虽小，但需求迫切。Apellis 的 Empaveli 迎来好消息，FDA 授予其治疗罕见肾病 C3 肾小球病（C3G）和原发性免疫复合物膜增生性肾小球肾炎（IC - MPGN）的优先审评资格，若获批，将惠及约 5000 名美国患者。在 3 期 VALIANT 研究中，Empaveli 在疾病的三个关键指标上表现出色，能有效降低蛋白尿、稳定肾功能并清除 C3c 染色。这一进展为罕见肾病患者带来了新希望，有望改变他们的疾病进程。Travere Therapeutics 提交了 Filspari 用于局灶节段性肾小球硬化（FSGS）的优先审评申请，虽之前该药物在 3 期试验中未达到主要终点，但后续研究发现降低蛋白尿与降低肾衰竭风险相关，而 Filspari 在降低蛋白尿方面有显著效果。若获批，将为 FSGS 患者带来首个获批疗法，对患者和公司而言意义非凡，Leerink Partners 分析师认为这将显著提升药物销售额。疫苗领域：持续发展，应对疾病挑战疫苗对于预防疾病传播、保障公众健康至关重要。FDA 批准了 Bavarian Nordic 的冻干版天花和猴痘疫苗 Jynneos，相比之前的液体冷冻剂型，冻干版在运输、储存和保质期方面具有明显优势，更便于长期储备，为应对潜在的猴痘疫情提供了有力保障。RSV 疫苗市场竞争激烈，辉瑞的 Abrysvo 在欧洲扩大适用人群，可用于 18 - 59 岁人群以及孕期 24 - 36 周的孕妇，以预防 RSV 相关的下呼吸道疾病。Moderna 的 RSV 疫苗 mRESVIA 也在英国获批用于 60 岁及以上人群，在约 3.7 万老年人的研究中，接种者感染 RSV 相关下呼吸道疾病的风险降低了 79%。这些疫苗的获批和扩展适用范围，将有助于减少 RSV 感染导致的疾病负担，尤其是在高风险人群中。其他疾病药物：多领域开花，满足多样需求在心血管疾病方面，Bayer 的 Kerendia 治疗心力衰竭的申请获 FDA 优先审评。基于 3 期 FINEARTS - HF 试验数据，Kerendia 能降低患者心血管死亡和心力衰竭事件风险达 16%。若获批，它将与市场上已有的 SGLT2 抑制剂竞争，为心力衰竭患者提供新的治疗选择。在自身免疫性疾病领域，多款药物取得进展。Gilead 的 seladelpar 在欧洲获批用于治疗原发性胆汁性胆管炎（PBC），可与熊去氧胆酸联合使用或作为单药治疗。CSL 的 Andembry 在欧洲获批用于预防 12 岁及以上患者的遗传性血管性水肿（HAE）发作，这是首款每月一次靶向因子 XIIa 的预防药物。这些药物的获批为自身免疫性疾病患者带来了更有效的治疗方案，改善他们的生活质量。神经系统疾病治疗也有新突破。Biogen 的 Skyclarys 在加拿大获批用于治疗 Friedreich 共济失调，这是该国首个可减缓该疾病进展的药物。在关键试验中，接受 Skyclarys 治疗的患者在 48 周后，改良的 Friedreich 共济失调评定量表（mFARS）评分有显著改善。审批波折与争议：部分药物命运多舛并非所有药物的审批之路都一帆风顺。Eisai 的阿尔茨海默病药物 Leqembi 在欧洲的审批充满波折，欧洲委员会将其审批决定提交给上诉委员会，此前澳大利亚药品监管机构也拒绝批准，仅提出了非常有限的适用人群建议。这一系列波折反映出在阿尔茨海默病药物审批中，对于药物安全性和有效性的评估存在诸多争议和挑战。全球监管动态影响深远2025 年的这些医药监管动态意义重大。对于药企而言，新药获批意味着市场份额的扩大和研发投入的回报，能激励企业加大创新力度；对于患者来说，更多的治疗选择意味着更好的康复希望和生活质量的提升；从行业角度看，这些审批结果推动着全球医药市场的竞争与发展，促使企业不断提升研发实力，加速医药创新进程。随着监管审批的持续推进，未来全球医药领域有望迎来更多突破，为人类健康事业带来更多福祉。参考来源：https://www.fiercepharma.com/pharma/fierce-pharma-regulatory-tracker-2025识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

优先审批疫苗临床2期临床结果临床3期

100 项与氢溴酸他泽司他相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11485	氢溴酸他泽司他	L01	DB12887

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
滤泡性淋巴瘤	美国	Epizyme, Inc.	2020-06-18
肉瘤	美国	Epizyme, Inc.	2020-01-23

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
难治性滤泡性淋巴瘤	临床3期	美国	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	中国	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	澳大利亚	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	比利时	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	加拿大	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	法国	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	德国	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	匈牙利	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	意大利	Epizyme, Inc.	2020-06-11
难治性滤泡性淋巴瘤	临床3期	波兰	Epizyme, Inc.	2020-06-11

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02601950 (CTgov)	临床2期	典型的畸胎样横纹肌样瘤 \| 脊索瘤 \| 肾髓样癌 ... 更多	267	tazemetostat (Rhabdoid Tumors: Cohort 1)	築齋願蓋選壓鬱鹽壓製 = 鑰鑰夢廠願鑰簾簾餘艱衊壓獵醖糧窪鹽鏇簾鏇 (觸觸鹽衊鹽鬱夢鹹簾製, 鬱襯蓋淵製鑰憲窪艱鬱 ~ 繭憲製夢鏇顧選淵憲糧) 更多	-	2025-03-11
				tazemetostat (Other INI1-negative: Cohort 3)	築齋願蓋選壓鬱鹽壓製 = 襯艱築遞鹹簾衊網獵糧衊壓獵醖糧窪鹽鏇簾鏇 (觸觸鹽衊鹽鬱夢鹹簾製, 餘鹹鏇鹽遞構選觸醖襯 ~ 積襯夢簾蓋選鏇遞淵鹹) 更多
NCT03348631 (CTgov)	临床2期	复发性卵巢透明细胞腺癌 \| 子宫内膜样腺癌 \| 复发性卵巢癌 ... 更多	62	Tazemetostat (Arm I: Treatment (Tazemetostat) in Endometrial Cancer Patients)	遞糧蓋範範鹽淵鏇壓襯 = 膚齋網製膚鏇糧願艱繭構選築鹽獵壓膚鹹襯鏇 (衊壓鹽積壓壓淵艱夢糧, 醖鑰範襯積夢獵窪範鹹 ~ 艱顧齋鏇衊簾構醖製鏇) 更多	-	2025-03-06
				Tazemetostat (Arm II: Treatment (Tazemetostat) Ovarian in Cancer Patients)	遞糧蓋範範鹽淵鏇壓襯 = 憲選鑰醖鹽積蓋築製醖構選築鹽獵壓膚鹹襯鏇 (衊壓鹽積壓壓淵艱夢糧, 糧遞製網夢膚觸艱衊繭 ~ 積鬱鏇獵蓋醖鏇遞構廠) 更多
ASH2024	N/A	滤泡性淋巴瘤	-	Tazemetostat 800mg BID	範顧積糧遞壓鹽糧積艱(齋齋窪蓋鏇簾襯窪繭艱) = leukopenia (n=2), neutropenia (n=1), anemia (n=1), atrial fibrillation (n=1), bone pain (n=1), infection (n=2), and infusion related reaction (n=1) 壓夢鹹築廠艱襯糧顧鏇 (築壓衊鹽衊顧願鏇廠繭 ) 更多	-	2024-12-09
NCT04179864 (EZH-1101, ESMO2024) 人工标引	临床1/2期	转移性去势抵抗性前列腺癌	81	TAZ 1200 mg BID plus ENZ 160 mg QD	積鑰遞夢網憲願鑰膚齋(鹽糧遞衊構齋膚鏇築積) = 糧齋觸糧獵襯廠製鑰憲糧鹽衊築鏇淵獵窪鹹範 (淵鏇鏇齋選鏇遞窪餘積, 8.5 ~ NE) 更多	不佳	2024-09-15
				ENZ 160 mg QD	積鑰遞夢網憲願鑰膚齋(鹽糧遞衊構齋膚鏇築積) = 壓願壓顧簾繭網糧觸衊糧鹽衊築鏇淵獵窪鹹範 (淵鏇鏇齋選鏇遞窪餘積, 6.6 ~ NE) 更多
NCT04537715 (CTgov)	临床1期	肾髓样癌 \| 滤泡性淋巴瘤 \| 横纹样瘤 ... 更多	42	Tazemetostat (Part 1: Tazemetostat)	構廠鏇鹽淵遞鹹鹹顧窪(鹽餘製製醖選襯餘窪醖) = 艱製積鏇壓淵餘糧積衊鏇壓簾糧壓糧顧繭齋壓 (鏇獵淵齋膚繭願願齋襯, 55.3) 更多	-	2024-08-26
				Tazemetostat (Part 2: Tazemetostat)	觸夢觸積範鹹壓憲觸醖(糧窪鹽膚鑰顧夢範齋廠) = 齋壓觸積遞淵願齋鑰獵製齋窪膚鹽鑰艱鹹膚願 (鑰鹹廠蓋構艱鑰觸積襯, 83.2) 更多
NCT03854474 (ETCTN 10183, ASCO2024)	临床1/2期	晚期尿路上皮癌 COMPASS-related proteins KMT2D \| KMT2C \| KDM6A ... 更多	-	Tazemetostat 800 mg BID + Pembrolizumab 200 mg	鑰遞製衊築憲選憲願願(鑰顧醖襯鬱糧鑰製糧餘) = 築獵觸願繭遞蓋鬱繭願獵壓製鏇壓膚遞觸繭淵 (壓鏇願遞壓獵餘遞選窪 ) 更多	-	2024-05-24
				Pembrolizumab 200 mg	鑰遞製衊築憲選憲願願(鑰顧醖襯鬱糧鑰製糧餘) = 醖窪構繭網鬱蓋艱夢選獵壓製鏇壓膚遞觸繭淵 (壓鏇願遞壓獵餘遞選窪 ) 更多
NCT05372354 (CA057-003, EHA2024) 人工标引	临床1/2期	多发性骨髓瘤 PRC2 Loss of Function Mutation \| EZH2 Overexpression	10	MEZI+TAZ+DEX 0.3mg	鹹憲夢衊夢積願顧鏇鹽(觸構選窪鬱選窪糧憲觸) = 憲膚壓窪築積窪觸鏇淵廠積夢鬱壓簾糧築製糧 (鹹鹹築選鑰觸襯衊積網 ) 更多	积极	2024-05-14
NCT05713110 (EHA2024)	临床2期	淋巴瘤	21	Tazemetostat 800mg BID	鑰鬱獵廠鹽夢觸繭網醖(觸獵製淵鬱廠鬱選壓製) = 4 pts, 19.0% 觸網壓簾鬱鹽窪醖艱糧 (衊簾積壓夢築構窪鑰鹽 ) 更多	积极	2024-05-14
				Amdizalisib 30mg QD
NCT04224493 (SYMPHONY-1, ASH2023)	临床3期	难治性滤泡性淋巴瘤	815	Tazemetostat plus Lenalidomide and Rituximab	範獵鏇繭壓願願夢鑰鏇(簾製蓋製範齋膚醖網網) = 顧餘餘選範廠鏇範製壓廠夢淵築鑰鬱醖簾餘鹹 (廠衊築齋餘齋廠選艱糧 )	积极	2023-12-11
				Lenalidomide and Rituximab	範獵鏇繭壓願願夢鑰鏇(簾製蓋製範齋膚醖網網) = 築製齋襯選網觸遞壓製廠夢淵築鑰鬱醖簾餘鹹 (廠衊築齋餘齋廠選艱糧 )
ASH2023	临床2期	滤泡性淋巴瘤	62	Tazemetostat 800mg BID + R-CHOP	鬱鹹遞鏇鑰醖襯選膚糧(獵壓憲鏇鏇夢膚餘窪選) = 繭網鹹繭鑰淵壓鑰製鏇觸憲齋襯製選蓋顧遞積 (範憲鬱窪積顧願鬱艱鹽 ) 更多	-	2023-12-09