Alnuctamab(Alnuctamab) - 药物靶点：BCMA x CD3ε_在研适应症：系统性红斑狼疮_专利_临床

概要

基本信息

药物类型

双特异性T细胞结合器

别名

BMS-986349、CC 93269、CC-93269

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靶点

BCMA x CD3ε

作用方式

抑制剂、激动剂

作用机制

BCMA抑制剂(B细胞成熟蛋白抑制剂)、CD3ε agonists(CD3e molecule agonists)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Icahn School of Medicine at Mount Sinai

非在研机构

Celgene Corp.Celgene International II SARL

百时美施贵宝（中国）投资有限公司

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权益机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

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结构/序列

Sequence Code 10044025

来源: *****

Sequence Code 13032029

来源: *****

Sequence Code 13032037

来源: *****

Sequence Code 13032097

来源: *****

关联

6

项与 Alnuctamab 相关的临床试验

NCT07219563

/ Not yet recruiting临床1期IIT

Open-label, 4-Part Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Alnuctamab (BMS-986349/CC-93269) in Participants With Moderate to Severe Refractory Systemic Lupus Erythematosus

This study will assess the safety and preliminary efficacy of the bi-specific TCE, alnuctamab (known as BMS-986349, CC-93269, EM901), targeting BCMA in patients with moderate to severe SLE, refractory to standard-of-care treatments.

开始日期2025-12-01

申办/合作机构

Icahn School of Medicine at Mount Sinai

NCT06232707

/ Withdrawn临床3期

A Phase 3, Randomized, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Alnuctamab Compared to Standard of Care Regimens in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) - ALUMMINATE RRMM

The purpose of this study is to evaluate the efficacy and safety of alnuctamab compared to standard of care regimens in participants with relapsed or refractory multiple myeloma (RRMM).

开始日期2024-05-03

申办/合作机构

Celgene Corp.

NCT06163898

/ Active, not recruiting临床1期

A Phase 1b/2a, Multicenter, Open-label Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Alnuctamab in Combination With Mezigdomide in Participants With Relapsed and/or Refractory Multiple Myeloma

The purpose of this study is to determine the recommended dose and schedule, and evaluate the safety and preliminary efficacy of alnuctamab in combination with mezigdomide in participants with relapsed and/or refractory multiple myeloma.

开始日期2024-02-27

申办/合作机构

Celgene Corp.

100 项与 Alnuctamab 相关的临床结果

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100 项与 Alnuctamab 相关的转化医学

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100 项与 Alnuctamab 相关的专利（医药）

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6

项与 Alnuctamab 相关的文献（医药）

2025-05-01·Clinical Lymphoma Myeloma & Leukemia

Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives

Review

作者: Rasche, Leo ; Einsele, Hermann ; Waldschmidt, Johannes M ; Kortüm, K Martin

Despite significant advancements, multiple myeloma (MM) remains incurable, and there is still a pressing need for new therapeutic strategies with highly selective mechanisms of action and balanced off-target toxicity. In recent years, the development of "off-the-shelf" bispecific antibodies (bsAbs) has significantly enhanced our ability to treat relapsed or refractory MM. Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Meanwhile, the range of available bsAbs is rapidly expanding, offering patients and healthcare providers a broad selection of options that vary in target antigens, binding domains, construct designs, dosing regimens, and side effects. As linvoseltamab, alnuctamab, and ABBV-383 (all BCMA × CD3), as well as forimtamig (GPRC5D × CD3) and cevostamab (FcRH5 × CD3) progress through late-stage clinical development, emerging trispecific antibodies are now available that target either 2 different MM-associated antigens or provide additional co-stimulatory signals to prevent T-cell exhaustion. Despite this plethora of therapeutic options, resistance to bsAbs is an inevitability, and the optimal positioning of these drugs within the current MM treatment landscape remains to be determined. In this review, we examine the available data on all clinically accessible bsAbs, evaluating their potential, current limitations, and implications for efficacy and safety, with the aim of achieving deeper responses and longer overall survival for MM patients.

2024-09-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

Informing the Recommended Phase III Dose of Alnuctamab, a CD3 × BCMA T‐Cell Engager, Using Population Pharmacokinetics and Exposure–Response Analysis

Article

作者: Lamba, Manisha ; Hsu, Kevin ; Bar, Merav ; Gaudy, Allison ; Kiesel, Brian ; Godwin, Colin ; Osawa, Mayu ; Masilamani, Madhan ; Burgess, Michael

Alnuctamab, a B‐cell maturation antigen (BCMA)‐targeting T‐cell engager, has demonstrated encouraging antitumor activity in the phase I study CC‐93269‐MM‐001 treating patients with relapsed or refractory multiple myeloma. Identification of a recommended Phase III dose (RP3D) was a key objective, as such population pharmacokinetic (PopPK) and exposure–response analysis was critical. Intravenous (IV) alnuctamab was administered in fixed doses (0.15–10 mg) or in step‐up doses to a maximum 10‐mg target dose. Subcutaneous (SC) step‐up doses of 3 and 6 mg were followed by a target dose range of 10–60 mg. Concentration data from IV and SC alnuctamab administration was pooled and was well described by a two‐compartment PopPK model with first‐order absorption and elimination. Covariate analysis determined that the inclusion of baseline soluble BCMA (sBCMA) on clearance significantly improved model fitting. Individual exposure parameters were estimated from the final model to characterize exposure–response relationships. Switching from IV to SC administration improved the safety profile of alnuctamab by limiting the frequency of grade ≥2 CRS events. A significant exposure–CRS relationship was observed after the first SC dose, but not subsequent dose administrations. Exposure–safety analysis did not find a statistically significant relationship between increasing exposure and the probability of key safety events of interest. Logistic regression analysis for patients administered SC alnuctamab identified that increased exposure significantly increased the probability of response, although the additional benefit was minimal at exposures above 30 mg target dose. Considering the totality of exposure–response data, the clinical pharmacology assessment supported a SC RP3D of 3/6/30 mg.

2023-08-01·Advances in therapy

Bispecific Monoclonal Antibodies in Multiple Myeloma: Data from ASH 2022: A Podcast.

Article

作者: Landgren, Ola ; Nadeem, Omar

The introduction of novel immunotherapies has transformed the treatment landscape in multiple myeloma (MM). The addition of these agents has significantly improved patient outcomes; however, MM remains largely incurable, with heavily pretreated patients suffering from shorter survival times. To address this unmet need, the focus has shifted toward novel mode of action therapies, such as bispecific antibodies (BsAb), which simultaneously bind to immune effector cells and myeloma cells. Currently, there are several T cell-redirecting BsAb being developed that target BCMA, GPRC5D, and FcRH5. These BsAb show impressive clinical activity for the relapsed/refractory population targeted and will likely become an essential part of MM treatment protocols in the future. In this podcast, the authors summarize and highlight some of the T cell-redirecting BsAb currently in development for the treatment of relapsed/refractory MM with a focus on the data reported at the oral session for BsAb at the American Society of Hematology's 2022 meeting from clinical phase 1 and 2 studies. The six presentations reported the latest safety and efficacy data for the BsAb: talquetamab, elranatamab, teclistamab, forimtamig, and alnuctamab.

32

项与 Alnuctamab 相关的新闻（医药）

2025-03-10

·医药地理

NMPA批准辉瑞CD3/BCMA双抗获批上市

3月10日，辉瑞宣布CD3/BCMA双抗埃纳妥单抗（Elranatamab，商品名：易瑞欧）获国家药监局附条件批准上市，用于治疗既往接受过至少三种治疗（含一种蛋白酶体抑制剂、一种免疫调节剂和一种抗CD38单克隆抗体）的复发或难治性多发性骨髓瘤（R/R MM）成人患者。此次批准主要是基于单臂II期MagnetisMM-3研究以及中国单独的Ib/II期单臂研究MagnetisMM-8研究的积极数据。MagnetisMM-3研究结果显示，接受过多线治疗的R/R MM患者接受埃纳妥单抗治疗后，中位总生存期（mOS）为24.6个月，中位无进展生存期（mPFS）为17.2个月。此外，中位随访33.9个月时，患者的中位缓解持续时间（mDOR）仍未达到，DOR达到30个月的患者比例为61.0%。目前，全球共两款CD3/BCMA双抗获批上市，另一款为强生的特立妥单抗（商品名：泰立珂），该药物已于2024年6月在中国获批上市。此外，再生元的linvoseltamab已在欧美申报上市，还有艾伯维的Etentamig（TNB-383B）和BMS的Alnuctamab已进入III期阶段。 END 如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

上市批准临床3期临床2期

2024-12-16

·FierceBiotech

BMS keeps axing deals inked under old leadership, this time culling cell therapy pacts with Century, Immatics

Under CEO Boerner, BMS continues to peel back a string of deals made under former leader Caforio\'s leadership.\n Bristol Myers Squibb has terminated cell therapy pacts with two biotechs amid \"ongoing portfolio prioritization efforts” within the Big Pharma, one of the affected companies revealed in an SEC document.The cuts were disclosed in separate Securities and Exchange Commission (SEC) filings made by Century Therapeutics and Immatics.Philadelphia-based Century had entered a collaboration with BMS back in 2022 in which the partners were working to develop stem cell-derived, engineered natural killer cell and gamma delta T cell candidates for blood cancers. The Big Pharma paid out $150 million in cash and an equity investment, plus committed more than $3 billion in biobucks.Now, after reviewing its portfolio, BMS is terminating the entire deal “without cause,” according to an SEC document filed Dec. 12. The dissolution is effective March 12, 2025.The programs have stayed in discovery and early-preclinical stages, with Century “encouraged by the scientific progress on the programs,” according to the SEC document. The biotech, which is currently conducting a strategic review of its preclinical pipeline, said it will assess potential opportunities for the programs in acute myeloid leukemia and multiple myeloma.The termination is “disappointing, but okay,” analysts from Leerink Partners wrote in a Dec. 13 note. The BMS decision doesn’t change the analysts\' positive long-term view of Century’s cell therapy platform or lead program, a CD19-targeting autoimmune candidate in phase 1 testing, the Leerink team noted. Given the partial focus on multiple myeloma, the Leerink Partners team wrote that the termination may reflect BMS’ acknowledgement that competitive hurdles in the indication are too high to warrant significant investments in the space. Because of that, the Leerink analysts don\'t assume the termination indicates anything negative about Century’s platform.The reprioritization at the Big Pharma, while “unfortunate,” is consistent with recent pipeline decisions made under CEO Chris Boerner, Ph.D.—who replaced Giovanni Caforio, M.D., last year—that indicate “more judicious resource allocation on oncology assets,” Leerink\'s analysts wrote.Since Boerner has taken the reins, BMS has also dropped a deal related to Agenus’ TIGIT bispecific antibody and an agreement with Eisai for its antibody drug conjugate (ADC).German biotech Immatics can now be added to that list, too. BMS inked a deal related to Immatics’ T-cell engager development in 2022—an expansion of a 2019 pact that focused on an autologous T cell receptor-based therapy (TCR-T). The revised deal included multiple off-the-shelf TCR-T and CAR-T programs, plus an upfront payment of $60 million and the chance to make up to $700 million per program through milestone and royalty payments.In 2023, BMS expanded the deal once again, exercising an option on an unnamed TCR-T.The two pact expansions have now been discarded, effective March 12 of next year, according to Dec. 13 SEC documents. The initial 2019 agreement remains intact. Earlier this year, BMS also jettisoned a bispecific molecule it licensed from Immatics for $150 million upfront in late 2021.The Big Pharma has also discontinued two internal multiple myeloma programs this year, including a phase 3-ready BCMA bispecific called alnuctamab because the company’s “business objectives” changed and a latestage BCMA CAR-T due to slow patient enrollment.

细胞疗法抗体药物偶联物免疫疗法引进/卖出临床1期

2024-09-21

·生物制药小编

印度公司相中的最佳三抗？

印度仿制药公司Glenmark Pharmaceuticals似乎相中了业内潜在最佳的三抗。 Glenmark Pharmaceuticals是1977年成立的印度老牌仿制药企，近年来正在寻求转型，其瑞士盟友Ichnos Sciences之前就与Glenmark Pharmaceuticals达成了合作联盟，建立了一家合资公司Ichnos Glenmark Innovation。近日，Ichnos Sciences宣布，已在Nature Cancer发表关于该公司CD3/BCMA/CD38三抗ISB 2001的临床前数据。结果显示，ISB 2001比强生的teclistamab（CD3xBCMA双抗）更有效地缩小了小鼠的多发性骨髓瘤肿瘤，并杀死了人体组织中的癌细胞，引起的T细胞因子分泌更少，因此比现有多发性骨髓瘤双抗更有优势的治疗窗口。现有疗法的弊端近年来，BCMA双抗和BCMA-CAR-T已经改变了多发性骨髓瘤（MM）的治疗格局，但是现有疗法仍然存在一些弊端。特别是治疗过后的复发问题仍待解决。比如说，单药使用后就存在TAA表达下调，抗原丢失等问题，这类现象在CD38单抗daratumumab和BCMA-CAR-T中都能够观察到。靶标达异质性可能是导致问题的原因之一，一些低CD38/BCMA表达的异质性肿瘤就会在杀伤后扩增。一些MM细胞甚至会在BCMA-CAR-T治疗后发生BCMA阴性突变导致耐药性逐渐增加。另外，缓解深度似乎也是复发的关键因素。早先的荟萃性研究就表明，杀死微小残留病（MRD）阴性肿瘤是MM治疗成功的保障。为了解决这些问题，多靶点策略或许是这些问题的最佳解决方案，近年来CD3xBCMA双抗teclistamab+CD38单抗daratumumab的组合就被提上日程。CD38单抗无法清除的MRD就可能有赖于CD3xBCMA双抗teclistamab，反之亦然。相似的策略还有同时靶向BCMA和CD38的CAR-T。目前来看，多药联用已经展现出了较为优异的临床数据，联合方案可以获得较高的初始ORR，值得期待或许OS和PFS数据的读出。虽然如此，CRS（细胞因子综合征）问题一直是TCEs在人体内应用时的阻碍，尤其是当teclistamab+daratumumab共同应用时，更加应该担忧治疗窗口。患有严重或危及生命的CRS的患者需要重症监护，需要采取安全缓解措施。三抗ISB 2001的对应优势 ISB 2001运用了Ichnos Sciences的BEAT平台（基于T细胞受体的抗体的双特异性接合）能够将T细胞表面蛋白CD3的结合位点连接到抗体重链上，重链上同时兼有BCMA结合位点，Y型的另外一边重链则能够靶向CD38。相较于teclistamab+daratumumab的组合，ISB 2001在临床前的体外和体内数据都更为优异。相比于BMS已经放弃的alnuctamab以及强生的teclistamab，ISB 2001具有20-260倍的杀癌效力。为了进一步测试ISB 2001的杀癌能力，研究人员将人类骨髓瘤细胞移植到小鼠身上，并用抗体治疗。在0.1mg/kg的剂量下，ISB 2001完全根除了所有八只小鼠的肿瘤；同时，接受teclistamab治疗的小鼠没有完全消退，只达到了30.8%的肿瘤生长抑制。而在CRS问题上，ISB 2001也具有一定潜在优势，虽然细胞毒性上，ISB 2001比teclistamab高10-100倍，但ISB 2001在体外诱导了相似的细胞因子分泌。这表明T细胞活化和细胞溶解活性所需的TCR刺激浓度远低于CRS发生的阈值。这解释了为什么ISB 2001尽管细胞毒性高，但并未显著增加CRS的风险。因此理论上来说，ISB 2001有更大的治疗窗口。目前这家公司已经招募了20人的ISB 2001的I期临床，预计相关数据将在今年晚些时候发布。对于Glenmark来说，或许更值得担心的是市场和工艺，就在上个月BMS放弃了CD3xBCMA双抗alnuctamab，原因是市场竞争，疗效更优的ISB 2001是否能凭借性价比杀入未来市场值得一看。参考来源： Carretero-Iglesia, L., Hall, O.J., Berret, J. et al. ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells. Nat Cancer (2024). https://doi.org/10.1038/s43018-024-00821-1 https://iginnovate.com/2024/09/11/igi-announces-publication-in-nature-cancer-on-isb-2001-igis-innovative-trispecific-antibody-for-relapsed-refractory-multiple-myeloma/

免疫疗法细胞疗法

100 项与 Alnuctamab 相关的药物交易

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研发状态

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
多发性骨髓瘤	临床3期	中国	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	日本	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	阿根廷	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	澳大利亚	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	奥地利	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	比利时	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	巴西	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	加拿大	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	智利	Celgene Corp.	2024-05-03
多发性骨髓瘤	临床3期	捷克	Celgene Corp.	2024-05-03

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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


NCT06232707 (ALUMMINATE RRMM, EHA2024)	临床3期	复发性多发性骨髓瘤	466	Alnuctamab	憲獵鏇觸積積積獵憲積(繭願窪選鏇齋鬱鑰醖鹽) = 醖積鑰製醖鏇餘獵鏇製齋衊襯膚觸繭壓簾鑰廠 (遞願顧築觸壓廠網鹽鏇 ) 更多	积极	2024-05-14
NCT03486067 (Phase 1 First‑in‑Human Clinical Study, ASH2023)	临床1期	复发性多发性骨髓瘤	73	ALNUC (BMS-986349; CC-93269)	積壓糧壓餘夢廠襯鏇鑰(製簾顧網醖憲廠膚獵鏇) = 廠願鬱蓋糧蓋醖遞繭壓顧鏇觸範齋壓範衊鏇蓋 (簾廠觸蓋齋鑰醖鑰糧願 ) 更多	-	2023-12-09
ASH2023	N/A	多发性骨髓瘤	1,926	BCMA-directed BsAbs	積簾壓憲夢膚廠鏇鹽選(餘衊鏇壓網築淵膚艱蓋) = 積觸鹹衊選淵築廠願構壓膚鏇蓋獵齋選淵簾積 (繭鹽衊獵獵繭壓衊繭繭 ) 更多	-	2023-12-09
NCT03486067 (EHA2023)	临床1期	复发性多发性骨髓瘤	70	ALNUCTAMAB	壓築糧齋蓋網鏇糧構蓋(糧製繭齋膚醖膚築積願) = Any-G/G3-4 treatment-emergent adverse events (TEAEs) occurred in 99%/79% of SC pts; most common were CRS (56%/0%), neutropenia (49%/42%), infections (47%/10%), anemia (41%/25%), and thrombocytopenia (33%/14%) 壓餘製壓憲繭構淵顧積 (鏇窪廠顧艱醖蓋範獵構 ) 更多	-	2023-06-08
NCT03486067 (EHA2023)	临床1期	复发性多发性骨髓瘤	-	IV ALNUC	蓋鑰餘範廠餘膚餘膚鏇(糧築壓鑰膚憲鏇網繭鏇) = 製襯製鏇餘獵繭醖齋鏇餘築鹽網鏇齋艱選鬱醖 (壓積齋糧構製廠淵遞獵 )	-	2023-06-08
NCT03486067 (ASH 12022 \| ASH 22022) 人工标引	临床1期	复发性多发性骨髓瘤	70	Alnuctamab	選夢糧鬱衊蓋築鬱繭餘(鹹繭衊糧願製觸齋築鹹) = 鑰積網選衊構齋網構餘鏇鏇顧鏇艱範膚壓膚膚 (鬱構壓鹹鹹窪鏇窪選獵 ) 更多	积极	2022-11-15
NCT03486067 (EHA2020)	临床1期	复发性多发性骨髓瘤	30	CC-93269	齋糧餘壓積製顧製膚壓(淵壓鹽鹽艱顧鹽窪鏇夢) = CRS was reported in 23 (77%) pts, the majority of whom reported a maximum grade 1 (n=15 [50%]) or grade 2 (n=7 [23%]), and occurred most frequently with the first or second dose (n=30 of 37 events [81%]) 鬱鑰願壓夢餘築壓範獵 (觸範願選製廠繭顧遞選 ) 更多	积极	2020-05-14