更新于：2024-12-09

Lisocabtagene maraleucel

利基迈仑赛

更新于：2024-12-09

概要

概要

基本信息

药物类型

自体CAR-T

别名

anti-CD19-EGFRt-4-1BB-zeta modified CAR CD8+ and CD4+ T lymphocyte therapy、anti-CD19/EGFRt/4-1BB/zeta modified CAR CD8+ and CD4+ T lymphocyte therapy、CD19-directed chimeric antigen receptor T cell therapy

+ [6]

靶点

CD19

作用机制

CD19调节剂(B淋巴细胞抗原CD19调节剂)、T淋巴细胞替代物

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [1]

在研适应症

套细胞淋巴瘤慢性淋巴细胞白血病小淋巴细胞淋巴瘤+ [28]

非在研适应症

前体B细胞急性淋巴细胞白血病复发性 B 细胞急性淋巴细胞白血病

原研机构

Fred Hutchinson Cancer Research Center

Bristol Myers Squibb Co.

在研机构

Bristol-Myers Squibb Pharma EEIG

Celgene Corp.

Bristol Myers Squibb Co.

+ [3]

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2021-02-05),

弥漫性大B细胞淋巴瘤滤泡性淋巴瘤高级别B细胞淋巴瘤+ [1]

最高研发阶段(中国)-

特殊审评加速批准 (美国)、孤儿药 (欧盟)、优先审评 (美国)、孤儿药 (美国)

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序列信息

Sequence Code 133531

来源: *****

Sequence Code 133534

来源: *****

Sequence Code 133555

来源: *****

Sequence Code 133567

来源: *****

Sequence Code 133586

来源: *****

Sequence Code 171111

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关联

项与利基迈仑赛相关的临床试验

NCT06313996 / Not yet recruiting临床3期

A Global Randomized Multicenter Phase 3 Trial to Compare the Efficacy and Safety of Lisocabtagene Maraleucel (JCAR017/BMS-986387) to Standard of Care in Adults With Relapsed or Refractory Follicular Lymphoma (TRANSFORM FL)

The purpose of this study is to evaluate the efficacy and safety of Liso-cel compared to standard of care in adults with Relapsed or Refractory Follicular Lymphoma.

开始日期2024-03-29

申办/合作机构

Juno Therapeutics, Inc.

[+1]

NCT06205290 / Withdrawn临床3期

A Global Phase 3, Randomized, Open-label, Multi-center Trial Designed to Compare the Efficacy and Safety of Lisocabtagene Maraleucel vs Investigator's Choice Options (Idelalisib + Rituximab or Bendamustine + Rituximab) in Adult Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), Whose Disease Has Failed Treatment With Both BTKi and BCL2i Targeted Therapies (A Double Class Exposed Population)

The purpose of this study is to compare the efficacy and safety of liso-cel vs Investigator's Choice options (idelalisib + rituximab or bendamustine + rituximab) in adult participants with R/R CLL or SLL, whose disease has failed treatment with both BTKi and BCL2i targeted therapies.

开始日期2024-01-16

申办/合作机构

Juno Therapeutics, Inc.

[+1]

NCT05934448 / Recruiting临床2期IIT

A Phase II Trial of Pembrolizumab in Combination With Chimeric Antigen Receptor Therapy in Patients With Relapsed/Refractory Primary Mediastinal B-cell Lymphoma

This research study is evaluating the combination of drugs, pembrolizumab with chimeric antigen receptor (CAR) T-cell therapy, as a possible treatment for primary mediastinal B-cell lymphoma that has recurred after prior treatment.
The names of the study drugs involved in this study are:
- Pembrolizumab
Standard treatment will include:
CAR T-cell therapy (either axicabtagene-ciloleucel or lisocabtagene maraleucel)
Cyclophosphamide
Fludarabine

开始日期2023-11-15

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

100 项与利基迈仑赛相关的临床结果

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100 项与利基迈仑赛相关的转化医学

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100 项与利基迈仑赛相关的专利（医药）

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163

项与利基迈仑赛相关的文献（医药）

2025-01-01·EUROPEAN JOURNAL OF HAEMATOLOGY

Comparative Analysis of Bispecific Antibodies and CAR T‐Cell Therapy in Follicular Lymphoma

Review

作者: Talami, Annalisa ; Morabito, Fortunato ; Gentile, Massimo ; Martino, Massimo ; Martino, Enrica Antonia ; Nizzoli, Maria Elena ; Neri, Antonino ; Pozzi, Stefano

ABSTRACT:

The treatment landscape for relapsed/refractory follicular lymphoma (RR‐FL) is marked by a pivotal debate between chimeric antigen receptor T‐cell (CAR‐T) therapy and bispecific antibodies (BsAbs). While both CAR‐T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA‐5 study, underscore axicabtagene ciloleucel (axi‐cel)'s efficacy in treating RR‐FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso‐cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR‐FL patients. Thus, CAR‐T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost‐effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost‐effectiveness considerations are essential; while CAR‐T therapies incur higher initial costs, their potential for long‐term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR‐FL management strategies.

2024-12-10·Blood Advances

OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL

Article

作者: Sharman, Jeff P. ; Bachier, Carlos ; Kostic, Ana ; Vedal, Min ; Hoda, Daanish ; Bellomo, Courtney ; Yimer, Habte ; Fanning, Suzanne ; Maris, Michael ; Terebelo, Howard ; Cherry, Mohamad ; Freytes, Cesar O. ; Essell, James ; Courtright, Jay ; Varela, Juan C. ; Yuan, Brenda ; Ogasawara, Ken ; Mattar, Bassam ; Linhares, Yuliya ; Cross, Scott ; Avilion, Ariel ; Espinola, Ricardo

Abstract:

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB chimeric antigen receptor (CAR) T-cell product approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We present the OUTREACH primary analysis, evaluating the safety and efficacy of outpatient monitoring after liso-cel treatment at community sites in the United States. Adults with R/R LBCL after ≥2 prior lines of therapy received liso-cel. Outpatient vs inpatient monitoring was per investigator discretion. The primary end points were incidences of grade ≥3 cytokine release syndrome (CRS), neurological events (NEs), prolonged cytopenia, and infections. Efficacy was a secondary end point. Eighty-two patients received liso-cel (outpatient monitored, 70%; inpatient monitored, 30%). The median follow-up was 10.6 months (range, 1.0-24.5). In outpatients and inpatients, grade ≥3 CRS occurred in 0% and 0%, NEs in 12% and 4%, infections in 12% and 8%, and prolonged cytopenia in 33% and 32%, respectively. Among outpatients, 25% were never hospitalized after infusion, and 32% were hospitalized ≤72 hours after the day of infusion; the median time to hospitalization was 5.0 days (range, 2-310). The median initial hospitalization duration after liso-cel was 6.0 days (range, 1-28) for outpatients and 15.0 days (range, 3-31) for inpatients. Objective response rate was 80%, complete response rate was 54%, and the median duration of response was 14.75 months (95% confidence interval, 5.0 to not reached). OUTREACH is, to our knowledge, the first and largest study to prospectively assess CAR T-cell therapy with outpatient monitoring in community-based medical centers. Liso-cel demonstrated meaningful efficacy with favorable safety in patients with R/R LBCL. Data support the feasibility of liso-cel administration at community sites with outpatient monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT03744676.

2024-11-01·Transplantation and Cellular Therapy

Real-World Analysis of Barriers to Timely Administration of Chimeric Antigen Receptor T Cell (CAR T) Therapy in Diffuse Large B-cell Lymphoma

Article

作者: Ehsan, Hamid ; Mesa, Ruben ; Elder, Jennifer ; Jennings, Rebecca D ; Pang, Yifan ; Ahmed, Ferdous ; Wallander, Michelle L ; Hu, Bei ; Copelan, Edward A ; Avalos, Belinda ; Yountz, Melissa ; Ghosh, Nilanjan ; Park, Steven ; Moyo, Tamara K ; Vaidya, Rakhee ; Howard, Dianna S ; Shroff, Vishal ; Wallander, Michelle ; Jacobs, Ryan W ; Beam, Travis ; Boseman, Victoria

The implementation of chimeric antigen receptor T (CAR T) therapy in the real-world setting is hindered by logistical and financial barriers, impacting timely access to this life-saving treatment. Clinical trials have reported the time from leukapheresis to CAR T cell infusion (vein-to-vein time) but not the time from CAR T referral to infusion (decision-to-vein time). Herein, we report the barriers to CAR T therapy in a real-world setting. We evaluated the factors influencing the decision-to-vein time and explored the association with clinical outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who received CAR T therapy. We conducted a retrospective study of adult patients with relapsed/refractory DLBCL who underwent consultation for CAR T cell therapy at Levine Cancer Institute and Wake Forest Comprehensive Cancer Center and collected information regarding demographic data, referral type, insurance type, CAR T product, and survival outcomes. The effects of variables on decision-to-vein time were analyzed by Fisher's exact test for categorial variables and Wilcoxon rank-sum test for continuous variables. Survival analyses were performed using Kaplan-Meier and Cox Proportional Hazard models. The study included 142 patients who were referred for CAR T of which 99 patients received CAR T. Median decision-to-vein time was 62 days compared to median vein-to-vein time of 32 days. Patients with private insurance took longer to obtain financial clearance compared to patients with government insurance (median 25 versus 9 days, P < .001). Of those with private insurance (n = 63), 35% needed a single-case agreement (SCA) which led to significant delay in receiving financial clearance (median 50.5 versus 19 days, P < .001) and increased decision-to-vein time (median 75 versus 55 days, P < .001) compared to those who did not need SCA. Decision-to-vein time was significantly different among various products, clinical trial being the shortest (median 47 days, n = 9) and non-conforming products being the longest (median 94.5 days, n = 6) (P< .001). Axi-cel had the shortest median decision-to-vein time at 61 days compared to 81 days with tisa-cel and 85 days with liso-cel. Although delays in receiving CAR T therapy did not impact survival, the median overall survival for patients who were referred for CAR T therapy but did not receive it, was significantly lower than those who received CAR T cell therapy (9.0 versus 21.0 months, P < .001). Decision-to-vein time is a major cause of delay in receiving CAR T therapy. SCAs lead to significant increase in decision-to-vein time leading to delays in CAR T therapy in a real-world setting. Patients who were referred for CAR T but are not able to receive it, have inferior survival compared to CAR T recipients. Our findings underscore the significance of addressing administrative hurdles, such as SCAs and insurance approvals, for timely access to CAR T therapy for patients with DLBCL.

502

项与利基迈仑赛相关的新闻（医药）

2024-12-05

·医药魔方

冲刺翻倍成功率！百时美施贵宝首席研究官Robert Plenge：最大化创新管线的研发效率

如何提升研发创新效率是制药界的一个永恒的难题，而且难度还在不断升级。一个不争的事实摆在眼前。尽管行业发展越来越成熟，产业分工越来越精细，但新药研发的周期却越拉越长，成本也水涨船高；同时面临着激烈多变的全球化竞争，新药的研发进度需要跻身全球前3或至少前5才有可能形成较明显的竞争优势。在这样的节奏和背景下，如何提升研发效率，打造出更多有临床和市场价值的产品管线，成为不同生态位的企业必须回答的命题。作为行业的领导者，百时美施贵宝（BMS）已经踏上了研发效率的跃升之路。一方面，BMS正在将早期研究和开发阶段的耗时减少近20%。另一方面，还在努力将临床开发的成功率从10%提升到20%。近期，BMS执行副总裁、首席研究官Robert Plenge在接受医药魔方采访时更深入地分享了点燃研发效率背后的5大研发原则，以及BMS基于5大原则进行内部研发和外部合作的模式。 BMS执行副总裁、首席研究官Robert Plenge 高质量研发的5大底层逻辑从研发管线到产品组合，可以看出BMS正在把研发引擎运转到某种极致 —— 在重点聚焦的5大核心治疗领域，始终有变革性药物的问世。肿瘤学领域，O药、Y药开创了免疫肿瘤的治疗时代。全球首个红细胞成熟剂罗特西普、两款CAR-T产品Abecma和Breyanzi填补了血液学领域很多未尽之需。全球首个TYK2变构抑制剂氘可来昔替尼片、S1P受体调节剂奥扎莫德则强化了BMS在免疫学领域的布局。心血管疾病领域，全球首创心肌肌球蛋白抑制剂玛伐凯泰打破了肥厚型心肌病近半个世纪的治疗困局。此外，随着数十年来首个全新机制精神分裂症疗法KarXT在美获批，BMS也迈出了重建神经科学领域先锋力的关键一步。诚然，创新存在着各种不确定性，而BMS能够持续输出高质量创新的秘诀在于 —— 明确的底层逻辑。 “第一，我们以对人类生物学因果关系的深刻理解为基础，从靶点开始药物发现之旅。其次，是药物的治疗模态与分子作用机制的相匹配。第三，我们专注于连接研究与开发，了解临床概念验证的路径，即首次看到药物是否达到预期效果。第四，一旦取得临床概念验证之后，我们就会尽快地加速临床开发，尽快地获批尽可能多的适应症。最后，确保‘以患者为中心’的市场准入工作可以使我们的创新药能够尽快地进入更多的市场，惠及更多的患者。” BMS的底层逻辑就是Robert介绍的5个端到端的原则，融合了BMS对于生物学、转化医学、临床开发和商业市场的深入理解。通过多学科交叉智慧凝炼而成的5大原则已经在BMS深入人心，是“所有人在研发工作中所共同信奉的”。这背后更深的意味是，参与每项研发的每个人都会纵观整个研发历程，而不仅仅局限于自身所负责的工作。“负责研究的工作人员要懂得临床开发和商业化运营，负责临床开发的工作人员也需要了解早期研究和商业化工作的复杂性。”有了坚实的共识和多元化的视角作基础，内部的协同合作便是水到渠成的事。早期研究与临床开发是新药研发链条上环环相扣的两大要素。为了保证这两个部门工作的紧密衔接，BMS构筑了粘性更强的架构体系。“我们会确保研究团队中有来自临床开发和商业化团队的成员。同样地，在临床开发的团队中也有来自研究以及商业化团队的成员。” 这种多元交融的合作体系也被充分应用在决策端。BMS内部有两个重要的决策委员会：一个决策哪些研究发现可以进入到早期开发，由Robert和BMS首席医学官赫思鸣（Samit Hirawat）共同担任主席；另一个负责全面开发阶段的决策, 由赫思鸣和首席商务官Adam Lenkowsky担任主席。“在整个过程中，BMS的领导团队都会了解正在研究和开发的项目，并就这些项目的价值和质量提出意见，以确保可以听到多元化的声音，从而根据正确的意见做出合理的决策。” 谈及如何确保在早期研究阶段就做出最佳决策，Robert总结了几个关键词：5大原则、人才团队和内外部合作。所有的决策都由人做出，从某种意义上而言，人决定了企业的创新走向。在Robert看来，“BMS拥有业界最优秀的人才”。BMS所取得的所有成绩，都是由这些人成就的。同时，这些人也串联起内外部的创新合作。 “最重要的是，我们始终坚持‘以患者为中心’，时刻关注患者未被满足的医疗需求，确保我们研发并提供的药物，能够为包括中国在内的全世界患者带来获益。” 研发版图中活跃的中国力量背靠全球化运营体系，越来越多的跨国药企不仅发力加速把全球新药惠及中国患者，也谋求将更多源于中国的创新带向世界。BMS“中国2030战略”中就明确提出，要致力于成为“根植中国、源于中国”的创新领导者。要尽早尽快地引入全球创新产品或适应症，就必须在研发过程中前瞻地融入中国患者的需求。BMS很早就洞悉到满足中国患者需求的重要性，并从战略层面进行贯彻。“在BMS的‘中国2030战略’中，我们希望扩大中国患者参与我们注册临床试验的人数，目标是让每一个临床试验都有中国患者的参与。” 这一战略目标，实际上也体现了BMS 5大原则在中国的深度实践。“它主要符合第4和第5条原则，即加快临床开发，尽快地将我们的创新药物惠及尽可能多的患者。” Robert表示。而对于前3项原则与中国市场的关联，Robert这样总结：“我们在不同人种的患者间开始人类生物学因果关系的研究，并在多元化的患者群体中进行临床概念验证研究，这其中就包括中国患者。我们推动治疗模态成为可能，无论其源自BMS还是合作伙伴，而这些合作伙伴也可能来自中国。” 以BMS与中国企业的合作为例：去年底，BMS与百利天恒子公司SystImmune就一款潜在同类首创EGFR×HER3双抗ADC药物BL-B01D1达成独家许可与合作协议。在这项合作中，“所有的研究工作都是由SystImmune完成的，他们发现了这两个靶点，并针对其构建相应分子，并完成了早期的概念验证。”而BMS则将和SystImmune一起发挥在实体肿瘤领域的专长，共同判断和决定哪些适应症和患者群体更有可能从这款药物中获益。 “我们现在已经看到一些非常让人兴奋的早期证据，可以证明这个药物的疗效。我觉得这也是一个很好的例子，显示我们是如何将源于中国的创新带向世界，造福全球范围内的患者。” 中国创新在ADC赛道的崛起，从BL-B01D1上就可见一斑，而Robert捕捉到了更多变化：“近年来，中国出现了越来越多的创新，覆盖到了很多治疗领域，涉及很多不同的药物类型。而且这些创新不仅来自于医院、大学，也来自于企业和风险投资。” 多元化创新的涌现，象征着中国的创新生态正在不断进化，并逐渐与全球接轨，这吸引着跨国药企不断加码、赋能中国创新。今年2月，BMS与环码生物达成一项可行性研究合作，探索环形RNA技术在某治疗领域应用的可行性。 10月，BMS连续第二年在中国举办了“中国合作周”。包括公司董事会主席、首席执行官博科思（Christopher Boerner）、Robert以及多位业务发展和研发部全球负责人一同现身合作周中的创新日论坛，足见BMS在中国寻求创新合作的诚意。借此交流平台，BMS再次向业界传递出合作之声，希望通过与中国生物医药产业生态圈各方的紧密合作，整合在肿瘤学、血液学、免疫学、纤维化、心血管疾病及神经科学等领域的创新实力，为更多患者研发并提供更多创新药物。研发目标：更多获益，效率翻倍 “双十定律”是对创新药艰难研发的高度概括，即一款新药需耗时10年，耗资10亿美元才能培育而成。而且，这种情况还在愈演愈烈。数据显示，近年来新药从发现到上市的研发周期可能长达10-15年，平均研发成本也呈螺旋式上升，已超20亿美元[1]。更残酷的是，高投入下的最终产出结果可能还是“九死一生”。这在行业里被喻为“超越披头士乐队”难题。Robert解释道：“如果好音乐的标准是每出一张新唱片就必须要超越披头士乐队的唱片，那恐怕就很难再有新的音乐可以产生了。现在我们也面临着同样的问题，因为很多现有的药物已经很不错了，新药物必须要被证明比已获批的药物更好才行。”正是因为要证明更优的获益，使得研发的周期延长，成本更高。以肿瘤学为例，“在结直肠癌中，有一种类型叫做微卫星高度不稳定性（MSI-H）结直肠癌。通过临床试验，我们发现O药加上Y药的‘免疫双子星’组合，在这一患者群体中能够获得明显比现有治疗方案更好的疗效。” 今年10月，这一双免疫联合治疗方案获得国家药品监督管理局批准用于一线治疗MSI-H/dMMR结直肠癌患者。这是O+Y的该适应症在全球的首次获批，标志着BMS在中国实现了药物新适应症的“全球首发”。在免疫学领域，实现功能性治愈是该领域存在的未满足需求，也是激励BMS前行的目标。曾为风湿免疫科医生出身的Robert认为，长期服用免疫抑制类药物，可能会带来增加感染风险和癌症风险等副作用。因此，让患者摆脱免疫抑制类药物非常重要。瞄准功能性治愈的目标，BMS较透彻地研究了自免患者免疫记忆的人类生物学因果关系，进而打造了一款CD19 CAR-T疗法BMS-986353。目前，已经有一些初步的数据证明该疗法有重置自免患者免疫记忆的潜力。 I期临床研究（NCT05869955）显示[2]，4例系统性红斑狼疮患者的 SLEDAI评分、PGA和 HAQ-DI均显著改善，这些患者入组时均有严重的肾脏器官系统受累，并且对多种既往治疗无效。在研发效率上，BMS同样树立了严格的标准与目标。一方面体现在临床开发的成功率上。“一般来讲，所有临床开发项目中，约有10%最后会实现获批。我们希望可以将这个数字翻一倍，从10%提升到20%。” 另一方面是对研发速度的追求。“这个速度必须是在保持高质量的前提下实现的。我们已经看到，我们将早期研究和开发阶段的时长减少了近20%。”归根结底，研发效率的提升也是BMS遵循五大原则的胜利果实。最后，Robert总结道：“信奉这5大原则让我们拥有了整个行业中最好的管线之一，并且助力推进了BMS‘中国2030战略’的落地生根。” 参考资料： [1]https://greenfieldchemical.com/2023/08/10/the-staggering-cost-of-drug-development-a-look-at-the-numbers/ [2]https://acrabstracts.org/abstract/a-phase-1-multicenter-open-label-study-to-establish-the-preliminary-tolerability-efficacy-pharmacokinetics-and-pharmacodynamics-of-cc-97540-bms-986353-a-cd19-directed-car-t-cell-therapy-manufa/ 推荐阅读百时美施贵宝的BD智慧：战略上坚守、战术上灵活 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

细胞疗法免疫疗法

2024-11-21

·佰傲谷BioValley

狼疮CAR-T正在成为焦点

CAR-T细胞是一种备受瞩目的新时代治疗方法，随着其治疗潜力的不断展现，业内正在不断扩大CAR-T的治疗范围，包括肿瘤、传染性疾病、自身免疫性疾病等。而现在，自身免疫性疾病正在成为CAR-T治疗的下一个前沿领域。在美国风湿病学会（ACR）上，红斑狼疮CAR-T成为了全场焦点，包括百时美施贵宝（BMS）、Kyverna Therapeutics、Fate Therapeutics和Cabaletta Bio所披露的数据，都凸显了CAR-T治疗狼疮的潜力。百时美施贵宝（BMS）资产：CC97540 阶段：1期 CC-97540是一种CD19 CAR-T细胞，使用了与Breyanzi相同的结构，并使用了NEX-T工艺制造。Breyanzi是一款商业化CAR-T，被批准用于大B细胞淋巴瘤、慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）、套细胞淋巴瘤。 BMS在ACR上发表了CC-97540针对自身免疫性疾病的1期临床研究，该研究纳入了对糖皮质激素和免疫抑制剂反应不足的系统性红斑狼疮（SLE）患者。 ACR会议上，BMS的发言人表示，结果表明CC-97540显著改善了纳入的7名SLE患者的狼疮表现。截止11个月的随访点，所有患者均未接受其他治疗，没有新的疾病活动迹象。 B细胞在第8天完全耗尽，参与者的SLE活动减少，患者和医生都报告在输注后一个月内生活质量有所改善。接受治疗的患者仍处于无药物缓解期。在会议上，BMS重点报告了一名患者，该名患者在治疗后成功受孕并生下了孩子。大约1/3的狼疮女性患者具有导致怀孕问题的抗体。此外，还报告了一例3级免疫效应细胞相关神经毒性综合征，该事件已经得到完全解决。发言人表示，该疗法具有可控的安全性，没有意外的不良事件。在此前发布的ACR摘要中，仅报告了1例与CC-97450相关的1级细胞因子释放综合症，且在1天内自行缓解，无需抗细胞因子治疗或类固醇。3/4（75%）患者观察到3级或4级的暂时性淋巴耗竭相关细胞减少症。没有报告神经毒性、严重不良事件（SAE）或剂量限制毒性（DLT）。目前，CC-97540正在进行两项多队列1期研究，以评估CAR-T在SLE、特发性炎症肌病和系统性硬化症的安全性、耐受性和有效性。 Kyverna Therapeutics 资产：KYV-101 阶段：1/2期 KYV-101是一款CD19 CAR-T，也是最早进入临床的自免CAR-T产品之一。在ACR 2024上，Kyverna报告了KYV-101在6名以目标剂量治疗的狼疮肾炎患者中显示出具有持续的疗效和持久性。正在进行1/2期试验发现显示，深度B细胞耗竭、免疫系统重置、SLE活性降低、肾功能保留和 eGFR（肾脏损伤的指标）稳定。所有患者都能够停止免疫抑制剂治疗并减少糖皮质激素。然而，在今年早些时候Kyverna披露的数据当中，低剂量队列中的一名狼疮患者在5个月后出现了疾病复发。延伸阅读：CAR-T的自免临床进展Fate Therapeutics 资产：FT819 地位：1期 FT819是一款iPSC来源的通用CD19 CAR-T细胞，其抗CD19嵌合抗原受体“1XX CAR19”由CD28共刺激域和改良的CD3z信号域组成，同时敲除了TRAC基因。 FT819最开始是被开发用于血液肿瘤治疗，现在扩展到自免疾病领域。 Fate公司报告了入组的首例狼疮性肾炎患者数据，该名患者患有严重疾病，自接受FT819以来，患者获得临床缓解。随访6个月后，患者的狼疮疾病活动度较低，无需任何免疫抑制治疗。值得注意的是，FT819正在与不含氟达拉滨的预处理一起给药，氟达拉滨通常作为清淋的组成药物，可能会增强自免患者的疗效。Cabaletta Bio 资产：CABA-201 阶段：1/2期 CABA-201是一款CD19 CAR-T细胞，目前正在进行4项CABA-201的1/2期临床研究，包括系统性红斑狼疮（SLE）、肌炎、系统性硬化症和全身性重症肌无力等适应症。其针对SLE的1/2期试验刚刚开始，目前仅有一名患者进行给药。 Cabaletta报告，首位患者在第15天观察到B细胞快速耗竭，输注后1-3个月观察临床改善。Cabaletta认为该结果很有希望。不过，在早些时候Cabaletta曾报告CABA-201针对狼疮患者的临床研究中，经历了一起4级的神经毒性事件，该事件也为CABA-201带来了安全性质疑。延伸阅读：搞出4级神经毒性，股价大跌34% 除了以上四家公布了临床数据，还有不少公司在ACR 2024年会上发布了自免CAR-T的临床前研究数据，包括来自西比曼的CD20/BCMA CAR-T、Capstan的体内CAR-T、Umoja的体内CAR-T。此外，国内长海医院团队还发布了同种异体CD19 CAR-NK治疗SLE的临床数据。小结狼疮是一种具有挑战性的疾病，治疗方法有限。尽管已经批准了一些靶向疗法，但是狼疮目前还是一种无法被治愈的疾病。现在，尽管CAR-T治疗狼疮还处于早期临床阶段，但是很多目光已经投向该方向，寄希望于CAR-T能够攻克狼疮治疗。参考资料： 1.https://www.biospace.com/drug-development/car-t-for-lupus-takes-center-stage-at-acr-2024 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

细胞疗法临床1期免疫疗法临床结果

2024-11-19

·Endpoints

Bristol Myers takes on autoimmune diseases with cell therapy, plus new data from Cabaletta and Kyverna

Bristol Myers Squibb recently presented for the first time data from its clinical trial of a cell therapy for autoimmune diseases, which has quickly become one of the most crowded fields in biopharma. Bristol Myers is developing an experimental cell therapy that uses the same construct as its approved blood cancer CAR-T treatment, Breyanzi, but with a shortened 5-day manufacturing process. The clinical study is still in its early days and includes people with several autoimmune conditions. So far, the company has reported clinical responses in all seven lupus patients with at least one month of follow-up. Bristol Myers, as well as the biotech companies Cabaletta and Kyverna, presented their respective clinical data over the weekend and on Monday at the American College of Rheumatology annual meeting. “There has been a burst of clinical studies in this field, and that’s very exciting,” said Georg Schett, the pioneering rheumatologist from the University Hospital Erlangen who first treated autoimmune patients with CAR-T cell therapy. “Nothing can grow within a day, right? It needs to be set up. But when you look at the field now, two years ago at the ACR, nobody spoke about cell therapy. And now this is really [something] everybody knows about.” Schett presented the Bristol Myers data at the conference and also sits on the scientific advisory boards of both Kyverna and Cabaletta. Safety of these cell therapies has become more closely watched after Cabaletta reported in August that a patient experienced grade 4 ICANS, which is a form of neurotoxicity associated with immunotherapy treatments like CAR-T cells. Bristol Myers also reported one case of grade 3 ICANS in a lupus patient that it said was “transient and resolved completely.” The patient experienced symptoms including “waxing and waning mental status” and “decreased level of consciousness,” according to the company’s presentation. But perhaps most intriguing was that one patient in the Bristol Myers study became pregnant within a few months after treatment. Schett highlighted that the case shows that fertility was not impaired by the conditioning treatment needed to receive the cell therapy. He added that the patient’s lupus did not flare up despite the fact lupus can be exacerbated in pregnancy. The patient was not taking any treatments for lupus after receiving the CAR-T cell therapy. The baby was born with normal counts of B and T cells. Cabaletta also shared new data showing that eight patients, including four lupus patients, treated with its cell therapy were able to stop immunosuppressants. As for Kyverna, it said Monday that it has now treated over 50 patients with its experimental CAR-T cell therapy across over 15 autoimmune conditions. But it’s actively running clinical trials for five diseases: lupus nephritis, systemic sclerosis, myasthenia gravis, multiple sclerosis and stiff person syndrome, its new CEO Warner Biddle told Endpoints News in an interview Monday. In lupus, it reported responses in all four patients who received its target dose of 100 million cells with at least 6 months of follow-up, and that none of the patients have required immunosuppressants following treatment. Kyverna also reported no cases of grade 3 or 4 cytokine release syndrome and no grade 2 to 4 ICANS across its 50+ patients. The company in September hired Biddle , who was previously head of commercial at Gilead’s cell therapy subsidiary Kite. Biddle said, “A big part of me coming to the organization is shifting the foundational work that we’ve done across these 50 initial patients, starting to focus in on the clinical trials that can get us to the first BLAs and getting access to a broader set of patients.” Kyverna expects to provide more details on its path to commercial approval in 2025 Biddle said.

细胞疗法临床结果免疫疗法临床研究ASCO会议

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外链

KEGG	Wiki	ATC	Drug Bank
D11990	-	L01XX	-

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
套细胞淋巴瘤	美国	Juno Therapeutics, Inc.	2024-05-31
慢性淋巴细胞白血病	美国	Juno Therapeutics, Inc.	2024-03-18
小淋巴细胞淋巴瘤	美国	Juno Therapeutics, Inc.	2024-03-18
B细胞淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2023-05-25
B细胞淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2023-05-25
B细胞淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2023-05-25
B细胞淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2023-05-25
难治性高级别 B 细胞淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2023-05-25
难治性高级别 B 细胞淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2023-05-25
难治性高级别 B 细胞淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2023-05-25
难治性高级别 B 细胞淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2023-05-25
大B细胞淋巴瘤	加拿大	Celgene, Inc.	2022-05-06
复发性弥漫性大B细胞淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2022-04-04
复发性弥漫性大B细胞淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2022-04-04
复发性弥漫性大B细胞淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2022-04-04
复发性弥漫性大B细胞淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2022-04-04
难治性弥漫性大 B 细胞淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2022-04-04
难治性弥漫性大 B 细胞淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2022-04-04
难治性弥漫性大 B 细胞淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2022-04-04
难治性弥漫性大 B 细胞淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2022-04-04

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
复发性套细胞淋巴瘤	申请上市	美国	Bristol Myers Squibb Co.	2024-01-30
复发性套细胞淋巴瘤	申请上市	日本	Bristol Myers Squibb Co.	2024-01-30
难治性套细胞淋巴瘤	申请上市	美国	Bristol Myers Squibb Co.	2024-01-30
难治性套细胞淋巴瘤	申请上市	日本	Bristol Myers Squibb Co.	2024-01-30
复发性滤泡性淋巴瘤	申请上市	美国	Bristol Myers Squibb Co.	2024-01-30
复发性滤泡性淋巴瘤	申请上市	日本	Bristol Myers Squibb Co.	2024-01-30
难治性滤泡性淋巴瘤	申请上市	美国	Bristol Myers Squibb Co.	2024-01-30
难治性滤泡性淋巴瘤	申请上市	日本	Bristol Myers Squibb Co.	2024-01-30
难治性慢性淋巴细胞白血病	申请上市	美国	Bristol Myers Squibb Co.	2023-11-18
复发性慢性淋巴细胞白血病	申请上市	美国	Bristol Myers Squibb Co.	2023-11-18

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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


NCT03331198 (TRANSCEND CLL 004, ASH2024) 人工标引	临床1/2期	慢性淋巴细胞白血病	118	Lisocabtagene Maraleucel (liso-cel) 50 × 10^6 CAR+T cells	繭鏇夢夢鹽鏇衊範壓醖(壓鬱廠壓鬱鏇窪衊網餘) = 網範夢簾顧願製範壓製壓衊築網網糧廠獵網構 (構夢構獵顧襯衊繭壓獵 ) 更多	积极	2024-12-09
				Lisocabtagene MaraleucelLisocabtagene Maraleucel (liso-cel)venetoclax (DL2 100 × 10^6 + PEAS + only prior BTKi exposure and were venetoclax naïve)	繭鏇夢夢鹽鏇衊範壓醖(壓鬱廠壓鬱鏇窪衊網餘) = 醖艱積鏇繭繭膚壓繭衊壓衊築網網糧廠獵網構 (構夢構獵顧襯衊繭壓獵 ) 更多
ASH2024	N/A	慢性淋巴细胞白血病	-	Lisocabtagene Maraleucel (liso-cel) + Ibrutinib (ibr)	艱窪製顧鹹築鑰簾糧窪(範醖憲齋鏇夢積淵繭鑰) = Any-gr CRS occurred in 45 (80%) pts (gr ≥ 3, n = 2 [4%]) 膚糧遞糧艱範簾鑰窪鑰 (獵艱淵衊壓構憲淵淵齋 ) 更多	-	2024-12-09
				Lisocabtagene Maraleucel (liso-cel)
ASH2024	N/A	难治性滤泡性淋巴瘤	-	Lisocabtagene Maraleucel (liso-cel)	衊網鑰衊積鑰糧壓獵網(鏇鏇壓齋襯淵鑰願觸獵) = 1% (no grade 4/5) 簾鬱蓋範築鹽夢製廠構 (鹹簾觸製廠夢獵襯糧鏇 ) 更多	-	2024-12-09
NCT04245839 \| NCT03105336 (ASH2024) 人工标引	临床2期	滤泡性淋巴瘤末线 \| 三线	101	Lisocabtagene Maraleucel (liso-cel)	淵夢夢積鏇顧餘願壓醖(膚獵積餘窪製鑰積襯網): RR = 1.25 (95% CI, 1.09 ~ 1.45) 更多	积极	2024-12-08
				Axicabtagene CiloleucelAxicabtagene Ciloleucel (axi-cel)
ASH2024	N/A	-	-	Lisocabtagene Maraleucel (liso-cel)	蓋築憲蓋網醖艱築鬱糧(遞簾餘鑰夢廠獵鬱鬱鏇) = mostly low grade, was reported in 64% of pts 鏇窪願積餘願壓繭遞蓋 (範遞顧範壓築糧積積繭 ) 更多	-	2024-12-08
ASH2024	N/A	-	-	Lisocabtagene Maraleucel (liso-cel)	廠鏇遞齋選壓觸繭衊壓(鹽餘艱顧醖築糧憲廠鹽) = 45% (grade 1, 37 pts; grade 2, 17 pts; 1 pt each with grade 3, 4, and 5) 鏇壓製鏇獵膚鏇選艱淵 (夢顧廠襯積構艱窪艱選 ) 更多	-	2024-12-08
ASH2024	N/A	-	-	Lisocabtagene Maraleucel (liso-cel)	壓蓋襯鹹築醖築衊夢鑰(壓鹹鹹獵範顧艱繭憲製) = any grade, 0.09 [0.04‒0.18]; grade ≥ 3, 0.09 [0.01‒0.75] 壓繭觸醖餘積鹽齋廠蓋 (齋蓋鹹夢製憲觸鹽範窪 ) 更多	-	2024-12-08
				Axicabtagene Ciloleucel (axi-cel)
ASH2024	N/A	-	-	Lisocabtagene Maraleucel (liso-cel)	製鏇簾膚遞鏇簾鹹簾願(選觸醖夢艱淵簾艱夢襯) = 簾鏇窪夢窪鑰網壓觸糧淵繭醖窪簾鹽顧餘鏇壓 (築艱積積製膚鬱糧觸糧, 45.1 ~ 58.5) 更多	-	2024-12-08
SOHO2024	N/A	-	-	Liso-cel	夢簾鑰糧遞遞網齋範選(齋淵糧願選夢衊鏇窪觸) = 鑰顧簾簾選選鏇鹹壓製繭鏇襯齋鑰願衊窪選鹹 (築簾願觸鬱鏇衊顧鑰餘 ) 更多	-	2024-09-04
SOHO2024	N/A	滤泡性淋巴瘤	-	Bridging Therapy (BT)	築鏇壓淵餘觸鹹蓋襯淵(廠獵構獵淵齋願製糧憲) = 襯遞鹽鹽糧獵繭艱選觸窪遞餘網壓蓋餘齋鏇顧 (醖範襯廠築築鬱獵製構 ) 更多	-	2024-09-04
				No Bridging Therapy (non-BT)	築鏇壓淵餘觸鹹蓋襯淵(廠獵構獵淵齋願製糧憲) = 艱鑰齋廠憲鏇鏇膚膚艱窪遞餘網壓蓋餘齋鏇顧 (醖範襯廠築築鬱獵製構 ) 更多