This phase I/II trial tests the safety, side effects, and best dose of tazemetostat and umbralisib and whether tazemetostat in combination with umbralisib and ublituximab works to shrink tumors in patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractor). Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Umbralisib may help block the formation of growths that may become cancer. Ublituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving tazemetostat in combination with umbralisib and ublituximab may work better in treating follicular lymphoma.

开始日期2023-05-01

申办/合作机构

City of Hope National Medical Center

[+1]

NCT04635683

/ Withdrawn临床1期IIT

A Phase I Trial of Lenalidomide, Umbralisib and Ublituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

This phase I trial studies the safety and how effective the combination of ublituximab, umbralisib, and lenalidomide is in certain types of indolent (slow-growing) non-Hodgkin's lymphoma or mantle cell lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Umbralisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Ublituximab is an antibody that attaches to the lymphoma cells and triggers immune reactions that may result in the death of the targeted lymphoma cells.

开始日期2022-09-30

申办/合作机构

Ohio State University Comprehensive Cancer Center

NCT04692155

/ Terminated临床1/2期IIT

Phase Ib/II Trial of Ublituximab and Umbralisib With CHOP (U2-CHOP) Followed by U2 Maintenance (U2-CHOP-U2) in Previously Untreated Mantle Cell Lymphoma (MCL)

This is a single arm, multi-center, open label Phase Ib/II trial in adult patients with newly diagnosed Mantle Cell Lymphoma (MCL)(Stage II-IV). The Diagnosis of MCL (Stage II, III, IV) is supported by histology and over expression of cyclin D1 or by FISH (fluorescent in situ hybridization). In the proposed study, the primary endpoint is to estimate the biological response rate of the combination of Umbralisib at dose 800 mg with Ublituximab (900mg)-Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP), but a phase Ib portion with dose de-escalation at two does level (800 and 600 mg) will be built in to further confirm its safety and tolerability. Treatment will be administered on an outpatient basis in 3-week (21 day) cycles. Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agreement.

开始日期2021-08-31

申办/合作机构

The University of Alabama at Birmingham

100 项与厄布利塞相关的临床结果

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100 项与厄布利塞相关的转化医学

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100 项与厄布利塞相关的专利（医药）

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项与厄布利塞相关的文献（医药）

2024-09-03·CLINICAL CANCER RESEARCH

PI3K Inhibitors in Hematology: When One Door Closes…

Review

作者: Skånland, Sigrid S. ; Okkenhaug, Klaus ; Davids, Matthew S.

Abstract:

The PI3K signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110γ and p110δ are highly enriched in leukocytes, providing an additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kδ inhibitor idelalisib was the first of four PI3K inhibitors (PI3Ki) to receive regulatory approval for relapsed B-cell malignancies. This was followed by approvals of the pan–class I inhibitor copanlisib (2017), the dual PI3Kγ/δ inhibitor duvelisib (2018), and the PI3Kδ and casein kinase 1ε inhibitor umbralisib (2021). Copanlisib and umbralisib received accelerated approvals, whereas idelalisib and duvelisib received initial accelerated approvals followed by full approvals. The accelerated approvals were based on overall response rates; however, follow-up studies showed increased risk of death and serious side effects. Furthermore, the confirmatory trial with copanlisib failed to show an improvement in progression-free survival when compared with chemoimmunotherapy. These developments led to black box warnings for idelalisib and duvelisib and withdrawal of copanlisib and umbralisib from the market by their manufacturers. Given the uncertain future of this drug class, additional manufacturers terminated ongoing phase III trials with novel PI3Kis. In this study, we review the development and current status of PI3Kis in hematology, limitations to their use, and our perspective on whether there is a future for PI3Kis in hematology.

2024-09-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Safety profile of first-line targeted therapies in elderly and/or comorbid chronic lymphocytic leukaemia patients (unfit subpopulation). A systematic review and network meta-analysis

Review

作者: Reczek, Monika ; Stożek-Tutro, Anita ; Kawalec, Paweł

This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton's tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.

2024-02-01·Clinical lymphoma, myeloma & leukemia

Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma

Review

作者: Wei, Michael C ; Bosch, Francesc ; Vassilakopoulos, Theodoros P ; Zumofen, Marie-Helene Blanchet ; Maio, Danilo Di ; Nastoupil, Loretta J ; Kuruvilla, John

BACKGROUND:

No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.

METHODS:

A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations. Imbalances in patient characteristics between NCT02500407 and studies featuring aggregate or patient-level data availability were accounted for using matching-adjusted indirect comparison (MAIC) and propensity score-based methodologies, respectively.

RESULTS:

ZUMA-5, ELARA, DELTA, DYNAMO, UNITY-NHL, AUGMENT and NCT01897571 passed the MAIC feasibility assessment. Patient-level data were available from GADOLIN, CONTRALTO and NCT02257567. MAIC results generally favored mosunetuzumab over tazemetostat in EHZ2wild-type patients for all outcomes and over PI3K inhibitors for complete response (CR), objective response rate (ORR), discontinuations due to adverse events and progression-free survival (PFS) with umbralisib. MAICs favored CART therapies for PFS and, to a lesser extent, ORR and CR. Comparisons with anti-CD20 antibody-based regimens yielded mixed results.

CONCLUSIONS:

ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2wild-type patients) and PI3K inhibitors and may be a promising alternative to re-challenging with a different anti-CD20 regimen in patients who relapse after ≥2 prior anti-CD20 lines. Although preliminary results somewhat favored CART therapies, limitations and uncertainties remain because of intrinsic differences in study design. Mosunetuzumab could thus be a promising treatment option for patients with RR FL after ≥2 prior therapies.

项与厄布利塞相关的新闻（医药）

2024-11-11

·药事纵横

FDA加速审批撤市药物盘点

1992年，FDA为应对HIV/AIDS流行而实施加速批准制度，使药物能够根据合理可能预测临床益处的替代终点获得批准。允许制药公司开始销售该药物，条件是他们必须进行验证性试验。自成立以来，该途径已帮助将近300种新药推向市场，其中许多用于治疗需求未得到满足的疾病。近期，辉瑞将其镰状细胞病治疗药物Oxbryta从全球市场撤下引起业内广泛关注，也引发了人们对该审评制度价值的担忧。本文总结了近年来五种已获得加速批准但后来退出市场的药物。 1.辉瑞的Oxbryta 批准时间：2019年11月撤回时间：2024年9月 Oxbryta是一种血红蛋白聚合抑制剂，于2019年11月获得加速批准，成为第一种专门针对镰状细胞病（SCD）根本原因的药物。通过增加血红蛋白对氧气的亲和力，从而抑制镰状血红蛋白聚合以及破坏红细胞镰状化。 2019年11月， FDA加速批准Oxbryta用于治疗成人和12岁及以上儿童SCD患者。2021年12月，FDA将Oxbryta的适用人群扩大至4岁及以上SCD患者。自2019年首次获得批准以来，Oxbryta已在全球超过35个国家获批上市。该药物最初由GlobalBlood Therapeutics开发，该公司于2022年被辉瑞以54亿美元收购。据辉瑞财报，2023年Oxbryta的全球销售额为3.28亿美元。 Oxbryta，也被称为Voxelotor，在欧洲药品管理局审查期间，一项涉及236名患者的试验中，治疗组有8人死亡，而安慰剂组有2人死亡；另一项针对腿部溃疡的研究中，88名患者中有8人死亡。2024年，辉瑞宣布自愿从目前已获批的市场中撤回所有批次的镰状细胞病（SCD）治疗药物Oxbryta，还将停止所有正在进行的Oxbryta的临床试验和全球扩展访问计划。辉瑞在一份声明中表示：“辉瑞的决定是基于临床数据，这些数据表明Oxbryta在SCD患者中的总体益处不再高于风险。数据表明，患者的血管闭塞危象和致命事件已失衡，需要进一步评估。” 尽管Oxbryta撤市，但患者现在有了更多的治疗选择，包括FDA去年批准的两种基因疗法Lyfgenia和Casgevy。 2.渤健和卫材的Aduhelm 批准时间：2021年6月停产时间：2024年1月 Aduhelm是近代历史上最具争议的批准之一，于2021年6月获得FDA批准，成为治疗阿尔茨海默病药物。在批准该药物时，外周和中枢神经系统药物咨询委员会强烈建议拒绝该药物，投票认为III期EMERGE和ENGAGE试验的证据不足以确定其疗效。 2021年6月7日，根据可使用生物标志物替代治疗终点的加速批准原则，FDA不顾独立专家委员会的反对，加速批准Aduhelm上市，并表示该药物适用于所有阿尔兹海默病患者，而不仅仅是临床试验所包含的早期阿尔兹海默病患者。这导致一名FDA专家委员会成员辞职抗议。由于前述种种争议，该药上市后业绩惨淡。在商业化成绩不佳的情况下，继续进行临床研究是一种负担。且该试验预计到2026年才能初步完成，需要投入费用不菲。另一方面，阿尔兹海默病赛道“追兵将至”，迫使渤健不得不将有限的资源投入Leqembi。该药物于2023年7月成为第一个获得传统FDA批准的抗β淀粉样蛋白治疗药物。2024年1月，全权负责该药物营销的Biogen停止了所有开发和商业化活动，以便将资源集中在Leqembi上。 3.武田的Exkivity 批准时间：2021年9月撤回时间：2023年10月 2023年10月2日，武田宣布，在经过了与FDA的讨论后，将与FDA合作，主动在美国撤回莫博赛替尼（EXKIVITY®，mobocertinib，中文商品名：安卫力）莫博赛替尼于2021年9月15日获FDA加速批准用于治疗含铂化疗期间或之后进展的、表皮生长因子受体（EGFR）20号外显子插入突变阳性（EGFRex20ins）的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。2023年1月，莫博赛替尼获NMPA附条件批准上市。该产品获批上市基于的是EXKIVITY1/2期单臂试验。2021年ASCO上公布的数据显示，铂基化疗组（PPP）中位OS（总生存期）达到惊人的24个月。尽管取得了惊人的疗效，但单臂试验毕竟不够充分，还需要3期确证性试验Exclaim-2的验证。然而，Exkivity在Exclaim-2试验未能证实有效，该公司于2023年10月自愿将Exkivity退出市场。 4.TG Therapeutics的Ukoniq 批准时间：2021年2月撤回时间：2022年6月同样在肿瘤学领域，TG Therapeutics的Ukoniq遇到了与辉瑞的Oxbryta类似的命运。在2021年2月获得治疗淋巴瘤的加速批准途径后，FDA于2022年6月撤回了该批准，因为更新的数据显示接受磷酸肌醇3激酶（PI3K）抑制剂治疗的患者的死亡风险可能增加。 Ukoniq对边缘区淋巴瘤和滤泡性淋巴瘤的批准是基于II期UNITY-NHL试验的总体反应率数据。但在2022年2月，在评估Ukoniq在相关类型癌症中的临床数据显示“服用该药物的患者死亡风险可能增加”后，FDA启动了一项安全性调查，并最终撤回批准。 5.吉利德的Zydelig 批准时间：2014年7月撤回时间：2022年1月另一种退出的PI3K抑制剂为吉利德科学的Zydellig。2014年获得加速批准，用于复发性滤泡性B细胞非霍奇金淋巴瘤（FL）和复发性小淋巴细胞淋巴瘤（SLL）患者的三线治疗。在FL中，数据显示总体缓解率（ORR）为54%，在SLL中，ORR为58%，缓解持续时间DOR为11.9个月。从而支持该批准。 2014年7月，Zydellig上市时携带有4项黑框警告，提示存在包括致命性肝脏问题在内的风险。2016年3月，Zydelig在临床研究中出现感染相关死亡等严重不良事件，先后遭到EMA和FDA的警告和调查。吉利德随后宣布暂停了Zydelig的所有临床研究，表示不再寻求将Zydelig开发成血液肿瘤的一线疗法。2022年年1月14日，吉利德自愿撤回Zydelig治疗FL和SLL的适应症，这款药物基本等同于撤市。目前，PI3K抑制剂的安全性已成为美国FDA极为担忧的一类药物。出于安全考虑，美国FDA咨询委员会建议停止PI3K抑制剂的单臂临床研究。加速批准途径主要依赖于可以预测后续临床益处的生物标志物，验证性试验经常被推迟。有42%在加速批准后需要一年多的时间才开始，或者尚未开始。且这些后续研究很少及时完成导致具有“潜在有害影响”和“没有足够益处”的药物可以继续在市场上销售。Oxbrtya已上市近五年，而吉利德科学的Zydelig已为淋巴瘤患者提供七年多。相比之下，生物标志物是罕见遗传病领域的可靠替代终点，它们代表了疾病的根本原因。因此，可以证明生物标志物与疾病原因之间相关性的遗传病可能更适用于加速批准途径。参考文献： Evolving FDA Accelerated Approval Pathway Suffers Spate of Withdrawals https://www.biospace.com/ 药事纵横征稿启事

加速审批基因疗法财报临床3期

2024-10-16

·生物制品圈

盘点 | 5款备受瞩目的曾获FDA加速审批但后被撤市的药物

加速审批通道于1992年为应对HIV/AIDS疫情而设立，它允许基于可能合理预测临床获益的替代终点来批准药物。制药公司可以在开展确证性试验的条件下开始销售该药物。自设立以来，该通道已助力近300种新药上市，其中许多用于治疗需求未得到满足的疾病。然而，近年来，该通道批准的药物中出现了多起备受瞩目的市场撤出和失败的验证性试验。比如，上个月辉瑞将其治疗镰状细胞病的药物Oxbryta从全球市场中撤出。实际上，这已成为一种日益明显的趋势：一些通过FDA加速审批通道上市的药物后来令人失望，有时甚至被撤出市场。在Oxbryta之前，已有渤健和卫材的首款阿尔茨海默病药物Aduhelm遭遇撤市。Aduhelm在获批后上市表现不佳，并引发争议，渤健于今年1月宣布停止销售。此外，还有其他一些通过加速审批通道上市的药物近期也被撤出市场。这些备受瞩目的反转事件引发了人们对该审批通道价值的担忧。美国食品药品监督管理局生物制品评价与研究中心（Center for Biologics Evaluation and Research，简称CBER）主任Peter Marks一直是该审批机制的坚定支持者。他在5月举行的美国基因与细胞治疗学会（American Society of Gene & Cell Therapy）会议上表示，在罕见病的情况下，“能够使用生物标志物或中间终点是初步越过终点线的有力方法。” 但近期，该通道受到了越来越多的审查。特别是2021年，FDA不顾其顾问委员会绝大多数成员投票反对，批准了Aduhelm的加速上市，这引发了诸多质疑。此外，确证性试验的完成一再推迟，也引发了人们的担忧，这促使FDA要求这些研究在加速批准之前已经在进行中。在该计划实施初期，大多数加速审批的药物都属于肿瘤学领域。耶鲁医学院医学与公共卫生学教授约Joseph Ross向BioSpace表示，他担心FDA的其他部门并未从肿瘤学部门来之不易的经验中受益：“我们基本上被迫重新学习肿瘤学部门在过去25年里所吸取的教训。” 这些教训包括避免确证性试验的延误，并关注临床结果。“替代标志物并不像人们认为的那样，能够很好地作为重要临床结果的替代指标，”Ross说。“看到CBER的负责人站出来，大胆宣称加速审批将如何被用来推动新的基因疗法上市以治疗罕见病，却没有考虑到肿瘤学领域几十年来所遇到的挑战，这令人沮丧”。下面，将介绍5种曾获得加速审批但后来被撤出市场的药物。 1、辉瑞的Oxbryta 批准时间：2019年11月撤市时间：2024年9月 Oxbryta是一种血红蛋白聚合抑制剂，于2019年11月获得加速批准，成为首个专门针对镰状细胞病（SCD）根本原因的药物。该药物最初由Global Blood Therapeutics开发，后者于2022年以54亿美元的价格被辉瑞收购。Oxbryta的获批时间比目标行动日期提前了三个月。近五年后，新数据显示接受治疗的患者死亡和并发症风险更高，辉瑞将所有全球市场中的Oxbryta撤市。据辉瑞称，Oxbryta的新安全性数据指出，患者“血管阻塞性危象和死亡事件之间存在不平衡”，这“需要进一步评估”。辉瑞最终确定，对于镰状细胞病患者而言，Oxbryta的总体获益“不再大于风险”。这一突然的撤市让医生和患者措手不及，尤其是考虑到镰状细胞病缺乏其他可用的治疗方案，镰状细胞病协会对药物研发领域20年来的进步付诸东流表示遗憾。 2、渤健和卫材的Aduhelm 批准时间：2021年6月停产时间：2024年1月 Aduhelm是近年来最具争议的批准药物之一，于2021年6月获得FDA批准，成为首个针对阿尔茨海默病潜在病因进行治疗的药物。在批准该药物时，FDA违背了其外周与中枢神经系统药物咨询委员会的意见，该委员会一致建议拒绝批准该药物，并投票认为III期EMERGE和ENGAGE试验的证据不足以证明其有效性。 2019年3月，在一项无效性分析显示Aduhelm无法达到其研究终点后，渤健和卫材最初放弃了该药物。然而，2019年10月，这两家公司宣布，由于该治疗药物达到了EMERGE试验的主要研究终点，他们将申请监管批准。 “我们认为加速审批途径非常适合这种情况，”FDA药品评价与研究中心（Center for Drug Evaluation and Research）主任Patrizia Cavazzoni当时告诉路透社，并补充说，“这允许药物在临床效益方面存在一些不确定性，同时让患者能够获得药物，而不必等待。” 但也有人持不同意见。上述咨询委员会的三名成员因对该批准表示抗议而辞职，Aduhelm在市场上也未能获得广泛关注。2024年1月，当时已全权负责该药物营销的渤健停止了所有开发和商业化活动，以将注意力集中在Leqembi上，该药物于2023年7月成为首个获得FDA传统批准的抗β淀粉样蛋白治疗药物。 3、武田的Exkivity 批准时间：2021年9月撤市时间：2023年10月加速批准途径已在肿瘤学领域得到了广泛应用，2022年批准的所有癌症药物中，有超过一半是通过这一途径获批的。 2021年，武田的酪氨酸激酶抑制剂Exkivity因在非小细胞肺癌（NSCLC）中显示出28%的总缓解率和24个月的中位总生存期，而获得了加速批准。Exkivity被特别批准用于治疗携带表皮生长因子受体（EGFR）外显子20突变的非小细胞肺癌患者。它是唯一一种获准用于治疗此类突变的口服疗法。然而，在Exclaim-2试验未能确认这些结果后，该公司于2023年10月自愿将Exkivity撤出市场。 4、TG Therapeutics的Ukoniq 批准时间：2021年2月撤市时间：2022年6月同样在肿瘤学领域，TG Therapeutics的Ukoniq遭遇了与辉瑞Oxbryta相似的命运。在2021年2月通过加速批准途径获得淋巴瘤治疗药物的绿灯后，由于更新后的数据显示，接受PI3K抑制剂治疗的患者死亡风险可能增加，FDA于2022年6月撤销了这一批准。 Ukoniq获批用于治疗边缘区淋巴瘤和滤泡性淋巴瘤，其依据是II期UNITY-NHL试验的总缓解率数据。但2022年2月，FDA启动了一项安全性调查，因为在评估Ukoniq治疗相关类型癌症的临床数据中，“发现服用该药物的患者死亡风险可能增加”。而评估Ukoniq治疗慢性淋巴细胞白血病患者的UNITY-CLL研究，由于报告的严重不良事件增加，引起了警报。 5、吉利德的Zydelig 批准时间：2014年7月撤市时间：2022年1月 Ukoniq撤市之后，另一种PI3K抑制剂——吉利德的Zydelig也遭遇了同样的命运。由于未能完成确认疗效和安全性的后续临床试验，吉利德于2022年1月将其从复发性滤泡型B细胞非霍奇金淋巴瘤（FL）和复发性小淋巴细胞淋巴瘤（SLL）市场撤出。 Zydelig于2014年获得加速批准，用于治疗FL和SLL的三线治疗患者。在FL方面，该批准得到了数据显示的总缓解率（ORR）为54%的支持。但缓解持续时间（DOR）无法评估。在SLL方面，ORR为58%，DOR为11.9个月。在撤市公告中，吉利德表示，由于“FL和SLL的治疗格局发生了变化”，完成确证研究的入组工作变得十分困难。一个值得注意的例外：Sarepta的Elevidys 有时，尽管一种药物在确证研究中未达到主要终点，但申办方和/或FDA可能会出于其他考虑而决定将其留在市场上。Sarepta Therapeutics的Elevidys就是这样一个例子，该药物于2023年6月获得加速批准，成为首个治疗杜氏肌营养不良症（DMD）的基因疗法。该批准适用于4至5岁能行走的儿童，其依据是数据显示该疗法增加了Elevidys的微肌营养不良蛋白的表达，这被认为是一个在该人群中合理可能预测临床获益的替代终点。然而，仅仅四个月后，Elevidys在III期EMBARK研究中未达到主要有效性终点，即与安慰剂相比，未能显著改善功能运动能力。尽管如此，Sarepta还是基于其所谓的“在所有预先规定的关键功能性次要终点中均表现出具有临床意义的治疗获益的强有力证据”，继续提交了标签扩展的申请。这一决策取得了回报，因为Elevidys在2024年6月获得了完全批准和标签扩展，用于治疗至少4岁的DMD患者，无论他们是否能行走。对于不能行走的患者，则根据一项正在进行的III期研究结果授予了加速批准。参考资料：5 Accelerated Approvals Gone Wrong.Biospace.October 14, 2024. 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点，不代表本站立场。

加速审批基因疗法细胞疗法

2024-09-19

·PRNewswire

Mantle Cell Lymphoma Clinical Trial Pipeline Insights Featuring 20+ Companies | DelveInsight

Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma originating from B-cells in the "mantle zone" of the lymph nodes. The development of novel targeted therapies and immunotherapies, such as Bruton's tyrosine kinase (BTK) inhibitors, is improving treatment outcomes and driving market growth for Mantle cell lymphoma. LAS VEGAS, Sept. 19, 2024 /PRNewswire/ -- DelveInsight's ' Mantle Cell Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mantle cell lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mantle cell lymphoma pipeline domain. Key Takeaways from the Mantle Cell Lymphoma Pipeline Report DelveInsight's mantle cell lymphoma pipeline report depicts a robust space with 20+ active players working to develop 22+ pipeline therapies for mantle cell lymphoma treatment. Key mantle cell lymphoma companies such as AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others are evaluating new mantle cell lymphoma drugs to improve the treatment landscape. Promising mantle cell lymphoma pipeline therapies such as Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others are under different phases of mantle cell lymphoma clinical trials. In May 2024, AstraZeneca had announced positive interim results from the Phase III ECHO clinical trial, which evaluated Bruton's tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) in combination with standard chemoimmunotherapy for treating mantle cell lymphoma (MCL). In March 2024, BeiGene, Ltd. announced the presentation of emerging oncology pipeline data at the American Association for Cancer Research (AACR) Annual Meeting. Additional highlights include preclinical characterization data for an investigational BTK degrader, BGB-16673, currently in clinical development for B-cell malignancies, including mantle cell lymphoma In October 2023, Ascentage Pharma announced that it has entered into a clinical collaboration with AstraZeneca Investment. The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca's Bruton's tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In January 2023, the FDA granted an orphan drug designation to LP-284, a novel small-molecule, next-generation acylfulvene, for the treatment of mantle cell lymphoma (MCL), a rare and aggressive form of B-cell non-Hodgkin lymphoma (NHL), according to an announcement from Lantern Pharma. Request a sample and discover the recent advances in mantle cell lymphoma treatment drugs @ Mantle Cell Lymphoma Pipeline Report The mantle cell lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mantle cell lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mantle cell lymphoma clinical trial landscape. Mantle Cell Lymphoma Overview Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphomas (NHLs) characterized by the (11,14) translocation, leading to overexpression of the cyclin D1 (CCND1) gene. Its various morphological variants can make diagnosis challenging, though some cases are straightforward. Many individuals with MCL are asymptomatic in the early stages, but may later seek medical attention due to persistent, typically painless swelling of lymph nodes, especially in the neck and throat region (e.g., Waldeyer's ring). MCL is marked by a reciprocal chromosomal translocation t(11;14)(q13;q32), which places the cyclin D1 gene next to the immunoglobulin heavy chain gene, causing continuous cyclin D1 expression. This overexpression contributes to tumor cell proliferation through cell cycle dysregulation, chromosomal instability, and epigenetic changes. Rarely, MCL cases without this translocation may involve CCND2 or CCND3 translocations. Hypothetical molecular subtypes, based on the cell of origin, correlate with clinical phenotypes: classical or aggressive MCL arises from naive B cells lacking or having limited iGVH mutations and expressing SOX11, a neural transcription factor inhibiting terminal B cell differentiation. The indolent variant originates from antigen-experienced B cells with IGVH somatic hypermutations, typically SOX11-negative and genetically stable. Diagnosis of MCL involves detailed patient history, thorough clinical evaluation, and specialized tests, including biopsy of an affected lymph node or bone marrow. These tests confirm the NHL type and subtype, assess disease extent, and determine appropriate treatments. Treatment for MCL is multifaceted and tailored to each patient, often including chemotherapy, immunotherapy drugs like rituximab, targeted therapies such as ibrutinib, and stem cell transplants, particularly for aggressive disease or younger patients. Radiation therapy may target specific lymphoma areas. Participation in clinical trials can offer new treatment options. Treatment plans are developed collaboratively by healthcare professionals and patients, considering disease stage, overall health, and personal preferences. Regular monitoring and follow-up care are essential to track treatment response and manage side effects effectively. Find out more about mantle cell lymphoma treatment drugs @ Drugs for Mantle Cell Lymphoma Treatment A snapshot of the Mantle Cell Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging mantle cell lymphoma pipeline therapies @ Mantle Cell Lymphoma Clinical Trials Mantle Cell Lymphoma Therapeutics Assessment The mantle cell lymphoma pipeline report proffers an integral view of the mantle cell lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Mantle Cell Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Apoptosis stimulants, Proto-oncogene protein c-bcl-2 inhibitors, Proteasome inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Agammaglobulinemia tyrosine kinase inhibitors Key Mantle Cell Lymphoma Companies: AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others Key Mantle Cell Lymphoma Pipeline Therapies: Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others Dive deep into rich insights for new drugs for mantle cell lymphoma treatment, visit @ Mantle Cell Lymphoma Drugs Table of Contents For further information on the mantle cell lymphoma pipeline therapeutics, reach out @ Mantle Cell Lymphoma Treatment Drugs Related Reports B-Cell Lymphoma Epidemiology B-Cell Lymphoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the B-cell lymphoma epidemiology trends. B-Cell Lymphoma Market B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including Vincerx Pharma, Ubix Therapeutics, Biomea Fusion Inc, Shanghai Hengrui Pharmaceutical, BeiGene, Hanmi Pharmaceutical, among others. Diffuse Large B-Cell Lymphoma Pipeline Diffuse Large B-Cell Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key DLBCL companies, including Genmab, Roche, Acerta Pharma, Autolus, Xynomic Pharmaceuticals, Genentech, Celgene, AbbVie, Mabion, among others. Diffuse Large B-Cell Lymphoma Market Diffuse Large B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including AbbVie, Genmab, Merck, Roche, Xencor and Janssen, Denovo Biopharma, Calithera Biosciences, IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期免疫疗法孤儿药

100 项与厄布利塞相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11322 D11323	厄布利塞	L01XE	DB14989

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	TG Therapeutics, Inc.	2021-02-05
边缘区B细胞淋巴瘤	美国	TG Therapeutics, Inc.	2021-02-05

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
弥漫性大B细胞淋巴瘤	临床3期	美国	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	澳大利亚	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	以色列	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	意大利	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	波兰	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	斯洛伐克	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	韩国	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	西班牙	TG Therapeutics, Inc.	2016-05-25
弥漫性大B细胞淋巴瘤	临床3期	英国	TG Therapeutics, Inc.	2016-05-25
套细胞淋巴瘤	临床3期	美国	TG Therapeutics, Inc.	2016-05-25

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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


NCT02742090 (CTgov)	临床2期	慢性淋巴细胞白血病	51	Umbralisib	積壓積膚獵廠顧憲淵網(醖廠範選積淵顧簾鹽齋) = 衊廠廠窪簾夢簾醖鹹選觸衊窪衊餘鬱醖遞鹹簾 (鏇壓淵選網積積鹽窪顧, 糧製繭範襯憲憲鬱願壓 ~ 構艱範窪憲鏇蓋窪齋蓋) 更多	-	2024-07-03
NCT02612311 (UNITY-CLL, CTgov)	临床3期	慢性淋巴细胞白血病	603	Ublituximab+Umbralisib (Experimental: Arm A: Ublituximab + Umbralisib)	醖夢選製顧繭遞淵選築(遞構構艱繭鬱窪襯淵鏇) = 襯鏇構築夢範鑰選餘襯廠齋膚鏇遞鏇獵餘窪壓 (艱簾網襯鹽膚艱範廠憲, 衊醖蓋網鏇鑰衊糧鹽觸 ~ 鬱艱鏇醖構廠積襯網憲) 更多	-	2024-05-07
				Obinutuzumab+Chlorambucil (Active Comparator: Arm B: Obinutuzumab + Chlorambucil)	醖夢選製顧繭遞淵選築(遞構構艱繭鬱窪襯淵鏇) = 窪簾醖淵壓窪蓋窪簾衊廠齋膚鏇遞鏇獵餘窪壓 (艱簾網襯鹽膚艱範廠憲, 願蓋蓋醖簾醖選膚糧鑰 ~ 選廠構膚鑰鏇觸鬱壓選) 更多
NCT03801525 (ULTRA-V, CTgov)	临床2/3期	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤	277	Ublituximab+Venetoclax+Umbralisib (Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V))	製簾製衊遞鹽製觸鹽顧(襯淵鏇膚醖鏇廠淵鏇構) = 淵餘餘願顧憲窪遞築積網簾夢鹽願夢獵蓋膚顧 (糧願網鹽膚壓構淵窪築, 膚襯願艱淵襯憲膚觸網 ~ 獵簾網鬱淵鹽憲膚廠糧) 更多	-	2024-04-19
				Ublituximab+Venetoclax+Umbralisib (Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V))	糧積獵繭餘積淵糧積鏇(簾製窪襯鹽繭襯製糧膚) = 觸鹹膚鏇鹽顧艱築願襯願遞鬱選願遞繭淵艱構 (鹽廠襯鬱憲蓋範憲餘構, 鏇壓醖窪遞鑰醖齋築襯 ~ 鏇觸膚築鏇顧獵衊醖範) 更多
NCT04624633 (ASH2023)	临床2期	慢性淋巴细胞白血病	29	Acalabrutinib	襯製觸憲蓋遞衊鑰繭鑰(鬱範齋顧蓋醖醖構醖簾) = 鬱鹹願選遞淵膚選窪築蓋獵膚積觸壓製襯積壓 (簾淵築醖鏇鹽蓋獵鑰選 ) 更多	-	2023-12-09
				Umbralisib	襯製觸憲蓋遞衊鑰繭鑰(鬱範齋顧蓋醖醖構醖簾) = 蓋醖遞衊範膚齋窪觸窪蓋獵膚積觸壓製襯積壓 (簾淵築醖鏇鹽蓋獵鑰選 ) 更多
NCT04783415 (CTgov)	临床2期	套细胞淋巴瘤	12	Ublituximab+Acalabrutinib+Umbralisib	鹹構鑰鑰構壓襯願簾積(築遞鏇壓糧淵網觸糧構) = 壓獵醖製觸鑰範製顧艱醖襯網範衊顧選觸觸艱 (醖築襯觸餘築齋蓋遞遞, 構鏇鏇築遞鬱窪選願繭 ~ 衊鹹襯醖鑰築獵築獵範) 更多	-	2023-11-18
NCT04508647 (CTgov)	临床2期	滤泡性淋巴瘤 \| 边缘区B细胞淋巴瘤	4	Ublituximab (Ublituximab Only)	淵蓋顧獵餘鬱鑰獵構鏇(觸顧範夢構簾觸襯衊製) = 壓鏇鑰積觸憲齋鹹築醖鬱範顧壓範繭廠繭廠簾 (網築顧衊鑰衊積餘範膚, 構遞鏇製鏇繭襯範蓋簾 ~ 製製夢壓網糧範鹽齋繭) 更多	-	2023-11-09
				Ublituximab+Umbralisib (Ublituximab First, Then Ublituximab and Umbralisib)	壓鏇憲鹽鬱夢齋獵鏇憲(網製簾選鑰艱夢網窪觸) = 鬱鏇憲壓鬱糧顧壓壓壓鏇壓製齋餘憲積積網膚 (鹽鬱選鑰網襯衊壓壓鹹, 網餘夢網鑰憲遞積鏇鑰 ~ 壓繭壓獵範餘廠憲選製) 更多
NCT04692155 (CHOP U2, CTgov)	临床1/2期	套细胞淋巴瘤	1	Ublituximab+Umbralisib	獵艱壓夢醖艱簾醖艱糧(淵簾窪窪鏇鹽獵夢觸觸) = 艱網蓋觸繭夢憲廠淵簾醖構鹽鹹壓顧鏇廠齋製 (衊淵製膚願簾淵衊蓋艱, 鏇壓鏇鏇鹹願遞鹽構衊 ~ 淵顧壓簾鑰醖願製製蓋) 更多	-	2023-09-28
NCT03828448 (CTgov)	临床2期	滤泡性淋巴瘤 \| 小淋巴细胞淋巴瘤	34	Ublituximab+Umbralisib	選鹽夢簾壓積憲膚壓壓(範鏇選艱範壓鏇廠壓蓋) = 鹽範夢蓋鏇餘網獵夢齋齋餘顧鏇構鏇範窪窪範 (窪淵齋製願齋窪顧遞餘, 糧積網憲艱齋淵壓願膚 ~ 網憲獵構築製餘積鹹鹽) 更多	-	2023-07-24
NCT04016805 (CTgov)	临床2期	慢性淋巴细胞白血病	41	Ibrutinib+Ublituximab+Umbralisib (Ublituximab + Umbralisib + Ibrutinib)	積衊餘淵憲鹽獵膚觸製(遞範網鏇鹹製製網艱衊) = 餘膚窪醖鏇簾構淵艱衊鹹範簾簾醖齋鏇獵鹽夢 (積鬱艱鏇夢衊鬱鏇蓋膚, 鬱構窪蓋築範壓襯鏇遞 ~ 簾網積糧夢餘繭鏇艱廠) 更多	-	2023-07-24
				Ublituximab+Venetoclax+Umbralisib (Ublituximab + Umbralisib + Venetoclax)	積衊餘淵憲鹽獵膚觸製(遞範網鏇鹹製製網艱衊) = 齋襯鑰築鑰網淵觸積糧鹹範簾簾醖齋鏇獵鹽夢 (積鬱艱鏇夢衊鬱鏇蓋膚, 鏇鹽憲構鹹鑰築衊簾憲 ~ 築窪壓製蓋遞壓鏇觸鬱) 更多