Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the adverse events and change in disease activity of etentamig in combination with a cereblon E3 ligase modulatory drug (CELMoD) agent in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease state will be assessed.
Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Multiple doses of etentamig in combination with iberdomide will be explored. Each treatment arm receives a different dose of etentamig and iberdomide to determine a tolerable dose. Approximately 135 adult participants with R/R MM will be enrolled in the study in approximately 50 sites worldwide.
In phase 1 participants will receive escalating intravenous (IV) etentamig in combination with oral iberdomide. In phase 2 participants will receive IV etentamig at one of two doses in combination with oral iberdomide, as part of the approximately 129 month study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and and monitoring of side effects.

开始日期2025-06-30

申办/合作机构

TeneoOne, Inc.

NCT06348108

/ Not yet recruiting临床1期IIT

A Phase Ib, Multi-center, Study of Talquetamab in Combination With Iberdomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

This phase I trial will evaluate the safety, side effects, and best dose of talquetamab in combination with iberdomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). There is currently a significant unmet need for patients with relapsed or refractory multiple myeloma (RRMM) who are triple class refractory and have been exposed to B-cell maturation antibody (BCMA) targeted therapy. These patients currently have limited treatment options and poor survival. Talquetamab is an FDA approved drug that can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug and works by targeting and destroying proteins that help myeloma cancer cells to survive. Dexamethasone is a corticosteroid, is similar to a natural hormone produced by the adrenal glands to reduce inflammation (swelling, heat, redness, and pain) and is used to in helping to treat certain types of cancer including myeloma.

开始日期2025-05-01

申办/合作机构

The University of California, San Francisco

[+2]

NCT06232044

/ Suspended临床1/2期IIT

A Phase I/II Study of the Safety, Tolerability and Efficacy of Belantamab Mafodotin (GSK2857916) in Combination With Iberdomide (CC-220)/Dexamethasone Versus Belantamab Mafodotin (GSK2857916)/Dexamethasone in Relapsed Refractory Multiple Myeloma

This phase I/II trial tests the safety, side effects, best dose, and effectiveness of iberdomide in combination with belantamab mafodotin and dexamethasone in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Multiple myeloma is a cancer that affects white blood cells called plasma cells, which are made in the bone marrow and are part of the immune system. Multiple myeloma cells have a protein on their surface called B-cell maturation antigen (BCMA) that allows the cancer cells to survive and grow. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Belantamab mafodotin has been designed to attach to the BCMA protein, which may cause the myeloma cell to become damaged and die. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.

开始日期2025-04-23

申办/合作机构

Alliance for Clinical Trials in Oncology

[+1]

100 项与伊伯多胺相关的临床结果

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100 项与伊伯多胺相关的转化医学

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100 项与伊伯多胺相关的专利（医药）

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项与伊伯多胺相关的文献（医药）

2025-06-02·CANCER RESEARCH

Targeted Degradation of Mutant p53 Reverses the Pro-oncogenic Dominant-Negative Effect

Article

作者: Gencel-Augusto, Jovanka ; Lozano, Guillermina

p53 is a transcription factor that functions as a tumor suppressor and the active unit of which is a tetramer. Nearly all cancers inactivate the p53 pathway, primarily through missense mutations in TP53. Most mutant p53 proteins lose their function and often exhibit increased protein stability. In addition to this loss of function, mutant p53 can drive oncogenicity through a dominant-negative effect by forming mixed tetramers with wild-type (WT) p53 to inhibit its activity. The study in this issue of Cancer Research by Klemm and colleagues provides definitive evidence for the mechanism by which mutant p53 inactivates WT p53 function. The p53R248Q mutant has a longer half-life than WT p53, resulting in an approximate ratio of 3 or 4 mutant molecules to every WT molecule. This imbalance facilitates the dominant-negative effect, which can be overcome either by exogenously increasing WT p53 levels or by selectively degrading mutant p53. In experiments whereby mutant p53 was degraded using a degron-tagged construct combined with iberdomide as a molecular glue, remarkable therapeutic efficacy was observed when this approach was used in combination with an MDM2 inhibitor. This work paves the way for therapeutic strategies that aim to degrade mutant p53 proteins in cases in which a WT TP53 allele is retained.See related article by Klemm et al., p. 1978

2025-06-01·ANNALS OF THE RHEUMATIC DISEASES

Responsiveness of systemic lupus erythematosus subjects to iberdomide based on molecular endotypes

Article

作者: Bachali, Prathyusha ; Lipsky, Peter E ; Daamen, Andrea ; Korish, Shimon ; Grammer, Amrie ; Schafer, Peter ; Hu, Yanhua

OBJECTIVES:

Iberdomide is a cereblon E3-ligase modulator that promotes proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) and was shown to be efficacious among subjects with generalised systemic lupus erythematosus (SLE). This study sought to identify baseline gene expression profiles of SLE subjects responsive to iberdomide and analyse the impact of this agent on gene expression.

METHODS:

Whole blood samples obtained from 276 female SLE subjects in the phase 2b iberdomide trial (NCT03161483) were assessed by RNA sequencing followed by gene set variation analysis (GSVA) using 32 informative gene modules. Unsupervised K-means clustering categorised subjects according to molecular endotypes at baseline. Each endotype was compared for treatment related gene expression changes.

RESULTS:

K-means clustering of GSVA scores from whole blood yielded 5 patient subsets (endotypes A-E) with increases in molecular abnormalities indicative of enhanced immune activity. Significant clinical responses to iberdomide, determined using the SLE Responder Index 4, were confined to endotypes C and E. The most important treatment related gene modules in responders in endotype E were Treg cells, B cells, and interferon, whereas unfolded proteins, oxidative phosphorylation and anergic/activated T cells were associated with responsiveness in endotype C.

CONCLUSIONS:

Molecular profiles of SLE subjects identified pharmacodynamic effects of iberdomide that occurred in all endotypes as well as changes in specific gene modules altered in endotypes associated with a significant clinical response. Thus, gene expression-based molecular profiling may be useful to enrich clinical trials for treatment-responsive subjects and also monitor the pharmacodynamic impact of therapy.

2025-05-16·ACS Chemical Biology

Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations

Article

作者: Keller, Aramis ; Gillingham, Dennis ; Zhanybekova, Saule ; Sauter, Basilius ; Lu, Xinyan

Cells with defective homologous recombination (HR) are highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibition. Current therapeutic approaches leverage this vulnerability by using PARP inhibitors in cells with genetically compromised HR. However, if HR factors in cancer cells could be inhibited or degraded pharmacologically, it might reveal other opportunities for synergistic combinations. In this study, we developed a model system that recapitulates PARP/HR synthetic lethality by integrating a small-molecule responsive zinc-finger degron into the HR factor Partner and Localizer of BRCA2 (PALB2). We further tested a series of peptide ligands for PALB2 based on its natural binding partners, which led to the discovery of a high affinity peptide that will support future work on PALB2 and HR. Together, our findings validate PALB2 as a promising drug target and provide the tools and starting points for developing molecules with therapeutic applications.

项与伊伯多胺相关的新闻（医药）

2025-07-14

·医药速览

ACS Med. Chem. Lett：基于 CRBN 的分子胶降解剂的理化性质优化【经验指南】

Early R&D Talking聚焦分子胶降解剂DOI: 10.1021/acsmedchemlett.5c00308侃侃而言学以致用结合 CRBN （一种常见 E3 连接酶）的分子胶降解剂临床上用于治疗癌症已有先例。针对“难成药”靶点，如转录因子，开发新一代高效降解剂，以满足不同适应症的需求正在激烈的竞争中。近日（Jul. 8），哈佛医学院在 ACS Med. Chem. Lett. 上发表评论，从微观视角探讨了通过物理化学特性来推进基于 CRBN 的分子胶降解剂的性质优化所采用的药物化学策略。药化策略：文中从极性、脂溶性、代谢稳定性等对药代动力学的影响，禅师了理化性质的优化策略；药物案例：IMiDs、CELMoDs;关键指标：LipE（脂溶性效率）、LipED（降解剂脂溶性效率）；新技术应用：共价锚定通过这些分享，为新一代降解剂开发提供了经验指南。01分子胶降解剂机制与发展1.1 分子胶降解机制免疫调节酰亚胺药物（IMiDs，如沙利度胺、来那度胺、泊马度胺）作为分子胶，可结合 E3 泛素连接酶复合体中的 cereblon（CRBN），重塑其表面，使其与新底物（neosubstrates）相互作用，进而可导致新底物的泛素化和蛋白酶体降解。典型的新底物具有一种称之为 G-环降解决定子的结构基序，由一个关键甘氨酸残基的 β-发夹构成，该甘氨酸残基介导三元复合物的形成，而在该位置的其它氨基酸会相互碰撞，阻止与新功能化的胶合剂-CRBN 表面结合。新底物通常为难成药的靶点，如锌指转录因子 IKZF1 和 IKZF3，它们的耗竭是IMiDs 治疗多发性骨髓瘤的基础。IMiDs 分子中极性戊二酰亚胺药效团与 CRBN 表面的沙利度胺结合域（TBD）的三色氨酸笼发生结合。比较流行的 PROTACs 通过将戊二酰亚胺类似物与目标蛋白（POI）的配体进行化学连接构建而来，从而提供一种模块化方法，诱导邻近效应实现 POI 降解。1.2 基于 CRBN 分子胶降解剂的发展与经验1.2.1 第一代：免疫调节亚胺类药物（IMiDs）IMiDs 是早期发现的分子胶降解剂，如沙利度胺、来那度胺、泊马度胺、阿瓦度胺，主要招募传统不可成药的锌指转录因子，如IKZF1/3，由于戊二酰亚胺的手性中心在 3-位上的快速外消旋化，使得 IMiDs 为外消旋混合物；解决这一问题，可以通过在戊二酰亚胺 3-位引入氘代交换氢原子来解决。如上图，在阿瓦度胺中应用，对映体可分离和单独分析，(S)-阿瓦度胺正在临床用于治疗多发性骨髓瘤和淋巴瘤的。研究 IMiDs 的物理化学性质，以及它们对体内 PK 和分布的影响，其中，泊马度胺与来那度胺相比，通常会认为额外的羰基基序可能会增加极性，实际上，泊马度胺的脂溶性大约是来那度胺的 10 倍。泊马度胺两个重要的分子特征，使其极性显著低于来那度胺（1）额外羰基碳原子sp2杂化，扩展了邻苯二甲酰亚胺环的 π 离域，增加了亲脂性；相反，来那度胺分离的苯酰胺基序（未形成 π 离域）增加了极性（上图中的圆圈），这一效应在电子结构中得到了反映。（2）泊马度胺额外的羰基氧与苯环上的氨基产生分子内氢键，这是来那度胺不可能具备的。此外，泊马度胺另一个显著的物理化学特征是，推-拉π电子效应，赋予了药物（及其类似物）固有的荧光特性，这甚至在临床上被用作患者血浆暴露的敏感标记物。极性对 IMiDs 的代谢的影响（1）高极性使来那度胺通过肾脏清除；而低极性的泊马度胺则是通过氧化代谢清除；因此，肾功能受损的患者需要调节来那度胺的剂量，以避免药物暴露过量带来的潜在毒性；（2）阿瓦度胺也具有显著的肾脏清除（给药的43%），可能是由于其氨基喹唑啉酮核心的极性所致，因此，肾功能受损的患者也要调整剂量。亲水性对 IMiDs 的 CNS 渗透性影响：来那度胺由于亲水性，因此其 CNS 渗透性较低，导致其难以进入 CNS 系统；这类药物没有像沙利度胺那样出现的镇静、神经病变等副作用。邻苯二甲酰亚胺和异吲哚酮降解剂性质的对比邻苯二甲酰亚胺的亲脂性是其异吲哚酮同类物的 6 倍，这意味着其渗透性（Caco-2 通量）提高了 4 倍，代谢速率（HLM Clint）提高了 2-3 倍，因此：（1）渗透性提高：若要提高异吲哚酮类降解剂的渗透性，可以将支架换为邻苯二甲酰亚胺；（2）代谢稳定性改善：用异吲哚酮替换降解剂的邻苯二甲酰亚胺核心，可以提高其代谢稳定性；当然，这些原则并非总是适用，但这些经验在基于性能的降解剂优化中具有一定的指导意义。1.2.2 新一代：CELMoDs（CRBN E3连接酶调节物）和 Cemsidomide邻苯二甲酰亚胺、异吲哚酮支架也被用来开发新一代 CRBN E3 连接酶调节化合物（CRLMoDs），包括 Iberdomide、Golcadomide、Mezigdo-mide，以及还有新一代降解剂 Cemisdomide。新一代降解剂相比于 IMiDs：（1）分子量更大、脂溶性更高，且含有吗啉、或哌嗪基团改善溶解性；（2）对 IKZF1/3 降解效率，能有效解决 IMiDs 治疗中因 CRBN 下调导致的耐药性问题；（3）外消旋化缓慢，可分离并纯化（S)-对映体用于临床；（4）新底物靶点扩展至 CK1α、IKZF2、GSPT1、VAV1、WIZ、WEE1等，适应症涵盖癌症、自身免疫病、镰状细胞病等。1.3 研究目的与重点这篇文章聚焦于基于 CRBN 的分子胶降解剂的理化性质和基于性质的优化策略，以推进其药物化学发展。重点探讨了如何通过调整理化性质（如亲脂性、极性、渗透性等）来优化分子胶降解剂的药代动力学（PK）和药效学（PD）特性。02基于理化性质的优化策略2.1 关键优化指标亲脂性效率（LipE）：用于衡量药物效力（IC50）与亲脂性的平衡，LipE 值越高，表明药物在保持效力的同时具有良好的药物性质。复合降解效力（CDP）：结合降解效力（DC50）和降解深度（Dmax）的指标，用于优化降解剂。其中，SF为缩放因子，在降解剂亲脂效率（LipED）中设置为 100，则：此前，研究团队还采用了另一个度量来描述降解剂的有效性，即蛋白质水平与药物浓度关系的曲线下面积（AUC），可以想象，也可以使用降解 AUC，生成类似的效率指标。2.2 案例分析案例1：CK1α降解剂从化合物 13到 SJ3149，通过将苯甲酰胺环化为杂环生物等排体，提高了代谢稳定性。案例2：IKZF2降解剂DKY709 和 PVTX-405，通过结构优化实现选择性降解 IKZF2，并改善溶解性和渗透性。案例3：GSPT1降解剂如 SJ6986 和 MRT-2359，具有口服生物利用度和类药性质。案例4：VAV1降解剂MRT-6160，具有优异的口服生物利用度和长半衰期，适用于神经自身免疫疾病。03创新技术3.1 共价锚定硫酰交换（CASE）在降解剂（如EM12）中引入磺酰氟弹头，通过共价结合 CRBN 的His353，显著提升结合力。通过磺酰交换反应，开发新的CRBN配体，如 CPD-2743，保留降解效力，消除致畸靶点SALL4结合，且渗透性提高（无外排）。3.2 新型弹头开发氟硫酸盐（EM12-FS）和磺酰咪唑（EM12-SO2Im）兼具高效标记 CRBN 与血浆稳定性，适合药物开发。04临床转化与挑战靶向蛋白降解剂，尤其是具有共价 E3 修饰作用的降解剂，相较于传统抑制剂具有更显著的药效学优势，因为只需对一小部分 CRBN 进行重新功能化就能实现对目标蛋白的高效催化降解。因此，药代动力学与药效学的不匹配可能使得相对高清除率的降解剂能够采用间歇性给药方案，从而降低达到有效浓度所需的 AUC 值，进而提高治疗指数。然而，对于此类策略而言，需要了解高游离 Cmax 所带来的风险，例如 hERG 毒性等，尤其是对于脂溶性和碱性降解剂而言，这似乎是临床候选药物普遍具有的物理化学特性。05总结与展望这篇文章系统阐述了通过理性设计理化性质（脂溶性、极性、稳定性），以优化CRBN分子胶降解剂的策略，结合创新技术，如共价锚定硫酰交换（CASE）和关键评价指标（LipED），推动其向更安全、高效的临床转化。理化性质优化是分子胶降解剂开发的核心，需平衡降解效力、PK、安全性；未来的关键挑战：解决高脂溶性候选物的脱靶毒性，扩大难成药靶点应用。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

蛋白降解靶向嵌合体临床结果

2025-07-05

·ioncology

2025 BOC/BOA丨贡铁军教授解析CARTITUDE-1与MIDAS研究：多发性骨髓瘤治疗新突破

点击蓝字关注我们编者按：2025年中国临床肿瘤学会年度进展研讨会（BOC）暨Best of ASCO 2025 China（BOC/BOA）于7月4日至5日在南京盛大召开。此次会议汇聚了国内外肿瘤学领域的顶尖专家，共同回顾并探讨过去一年中国临床肿瘤学的重大进展，并分享刚刚落幕的美国临床肿瘤学会（ASCO）年会的前沿成果。会上，哈尔滨血液病肿瘤研究所贡铁军教授带来了多发性骨髓瘤领域的重磅研究进展。《肿瘤瞭望-血液时讯》现场特邀贡铁军教授，针对这些前沿成果进行了深入交流，探讨了CAR-T治疗、MRD驱动策略等新兴疗法在骨髓瘤治疗中的重要意义及未来潜力。《肿瘤瞭望-血液时讯》：CARTITUDE-1研究数据显示，cilta-cel在复发/难治性多发性骨髓瘤患者中实现了长达5年的缓解和生存。作为国内CAR-T研究的重要推动者，您如何评价这一数据对未来CAR-T疗法持久性、安全性及再治疗策略的启示？贡铁军教授：CARTITUDE-1研究（摘要号：7507）在今年ASCO大会上进行了最新更新，取得了令人振奋的成果。首先，研究观察到患者中位总生存期（OS）达到了5年；同时，在接受一次CAR-T治疗后，约33%的患者能够持续缓解。随着免疫治疗的不断进步，多发性骨髓瘤患者的缓解深度持续加深，生存期显著延长。此外，CAR-T治疗最显著的获益之一是改善患者的生活质量。患者在接受一次治疗后无需持续治疗，从而能够重新融入社会，恢复正常的工作和生活。这为多发性骨髓瘤患者的慢性病管理提供了新的希望。研究简介（滑动查看）西达基奥仑赛注射液（cilta-cel）治疗复发/难治性多发性骨髓瘤（RRMM）患者的长期随访结果：CARTITUDE-1研究中5年缓解与生存数据背景：CARTITUDE-1研究评估了cilta-cel在重度预处理的RRMM患者中的疗效，这些患者通常预期中位无进展生存期（PFS）少于6个月（mo），中位总生存期（OS）约为1年（y）。在33.4个月的中位随访期后，中位PFS为34.9个月，中位OS尚未达到（36个月OS率为62.9%；Lin等，ASCO 2023）。本文报告了中位随访60.3个月，OS、≥5年无进展的结果以及安全性数据。方法：CARTITUDE-1研究中的患者接受了单次cilta-cel输注。利用药物制剂、基线和输注后的样本进行相关分析。患者在CARTINUE（NCT05201781）研究中继续随访，以评估进展、生存率和安全性，随访期为15年，至少每年进行一次评估。结果：97例接受治疗的患者中，有32例（33.0%）在接受cilta-cel治疗后≥5年仍然生存且无进展，并且未接受进一步的多发性骨髓瘤治疗。对于这32例患者，在CARTITUDE-1入组前，最后一次治疗（LOT）到疾病进展的中位时间为4.0个月（范围：0.7–48.6个月）。在这32例患者中，中位年龄为60岁（范围：43–78岁），中位既往治疗次数为6.5（范围：3–14），其中23.3%具有高风险细胞遗传学，12.5%有髓外病变（EMD），90.6%为三药耐药，46.9%为五药耐药。对于≥5年无进展的患者，其基线特征，包括具有高风险细胞遗传学和EMD的患者，与5年内发生进展的患者相似。与5年内发生进展的患者相比，与≥5年无进展相关的显著生物标志物包括：药物制剂中具有更高比例的初始T细胞、较低的中性粒细胞与T细胞比率、较高的基线血红蛋白和血小板水平，以及较高的效应细胞与靶细胞比率（Cmax与sBCMA）。在Cmax时，这些患者还具有显著更高的CD4中心记忆型CAR+T细胞亚群，以及活化标志物CD38、CD25和PD-1阳性的CAR+ T细胞也显著较高。在一个单中心的亚组中，进行本地连续的微小残留病（MRD）评估。该中心的12例≥5年无进展的患者，在10–6水平上为MRD阴性，且每年进行一次PET/CT影像学检查，结果均为阴性。结论：在CARTITUDE-1研究中，患者的中位OS为5年，33%的患者在单次cilta-cel输注后≥5年仍无进展。这些数据首次证实，cilta-cel可能对RRMM患者具有治愈潜力。上下滑动查看更多《肿瘤瞭望-血液时讯》：本次大会还选取了MIDAS研究作为重点讨论内容，能否请您分享一下选择该研究的原因及其背景？您如何看待MIDAS研究在多发性骨髓瘤治疗中的独特价值？贡铁军教授：MIDAS研究（摘要号：7500）是我们在本届 ASCO 年会上选取的另一项重要研究成果。选择该研究的原因在于，目前多发性骨髓瘤的治疗方向既包括将其转化为一种慢性病的长期管理，又涉及挑战传统治疗方法，如自体造血干细胞移植等。因此，我们希望通过四药联合治疗以及后期双药巩固治疗，探索其是否能为患者带来类似的临床获益。MIDAS研究的结果为我们提供了有力的证据。一方面，该研究实现了深度缓解，并维持了持续的微小残留病（MRD）阴性状态，从而有效降低了患者的复发率。另一方面，研究表明双次移植的治疗地位可能在未来会有所下调，前线采用多药联合方案，后续配合多药巩固治疗，有望为患者提供一种更为优化的治疗路径。此外，这种治疗策略在中国具有重要的现实意义。鉴于免疫治疗药物成本相对较高，倘若能够利用经济可及的药物实现有效的治疗，将使绝大多数患者能够承受并接受这种治疗方案，从而为广大中国患者带来显著的临床获益。基于上述因素，我们选择了该研究作为大会主旨发言的内容。研究简介（滑动查看）MRD驱动策略用于IsaKRD诱导后适合移植的新诊断多发性骨髓瘤（NDMM）患者：MIDAS III期临床试验的主要终点背景：III期IFM2020-02-MIDAS研究（NCT04934475）评估了适合移植的新诊断多发性骨髓瘤（NDMM）患者，采用艾沙妥昔单抗、卡非佐米、来那度胺和地塞米松（IsaKRD）诱导治疗后，基于微小残留病（MRD）的巩固与维持治疗策略。IsaKRD诱导阶段的结果已在之前的研究中发布（Perrot等，Blood，2025年）。本文将展示该研究在MRD驱动巩固阶段的结果。方法：MIDAS是一个多中心、开放标签、随机化的III期临床试验，纳入18-65岁、适合移植的NDMM患者。在诱导治疗后，达到10-5阈值MRD阴性的患者随机分配至两组：一组为6个IsaKRD治疗周期（A组），另一组为自体干细胞移植（ASCT）后进行2个IsaKRD治疗周期（B组），随后进行来那度胺维持治疗。对于诱导治疗后MRD阳性（MRD≥10-5）的患者，随机分配至单次ASCT加2个IsaKRD治疗周期（C组）或双次ASCT（D组），随后进行艾沙妥昔单抗加iberdomide维持治疗。随机化过程中按照细胞遗传学风险和中心进行分层，并在A组与B组比较时按照诱导后10-6的MRD阴性情况进行分层。主要终点为维持治疗前，达到10-6水平的MRD阴性（通过NGS检测）。结果：共有485例诱导后MRD阴性的患者随机分配至A组（243例）和B组（242例）。维持治疗前，A组和B组在10-6水平的MRD阴性率分别为84%和86%（OR 1.17，95%CI：0.64–2.76；P=0.64）。另外，233例MRD阳性（10-5）患者随机分配至C组（109例）和D组（124例），其中19例患者（15%）未接受计划中的双次ASCT。维持治疗前，C组和D组在10-6水平的MRD阴性率分别为40%和32%（OR 0.73，95% CI：0.42–1.25；P=0.31）。在巩固阶段，共有5名患者发生疾病进展（A组2例，B组0例，C组0例，D组3例），其中A组有2例患者无进展死亡。与诱导阶段相比，未发现新的安全性信号。该研究仍在进行中。在A/B组的中位随访时间为16.8个月，C/D组为16.3个月，持续MRD阴性和无进展生存期（PFS）数据尚未公布。结论：在进行6个IsaKRD诱导周期后，对于达到10-5 MRD阴性的患者，在维持治疗前，基于移植方案与单纯IsaKRD巩固治疗在10-6 MRD阴性率上无显著差异；而对于未达到10-5 MRD阴性的患者，双次ASCT未能显著提高维持治疗前的10-6 MRD阴性率。需要进一步的随访数据，包括持续的MRD阴性率和PFS数据，以评估该MRD驱动策略的长期疗效。上下滑动查看更多《肿瘤瞭望-血液时讯》：无论是CAR-T在复发难治阶段带来的长期生存希望，还是MRD驱动下前移的精准控制策略，您如何看待当前骨髓瘤治疗格局正在发生的变化？在中国临床环境下，我们应如何借助这些国际前沿成果加速治疗路径优化？贡铁军教授：多发性骨髓瘤的治疗可分为几个关键阶段。在初始阶段，我们的目标是确保患者能够存活，并尽可能延长生存期。进入第二阶段，我们希望能够将患者的治疗转化为慢性病管理。到了第三阶段，我们的治疗目标更进一步，力求不仅延长患者的生存期，还要保障他们的生活质量。免疫治疗的出现使得患者在延长生存期的同时，能够维持较好的生活质量。在此背景下，我们进一步探索是否能够通过MRD监测，在常规治疗下帮助患者达到最佳的生活状态和生存质量。目前，无论是在国际上还是国内，都在该方面进行了大量的临床研究，取得了令人鼓舞的成果。其中，前期采用四药诱导、巩固治疗，后续使用两药维持治疗，已使绝大多数患者的生活质量和无进展生存期（PFS）均得到显著改善，初步实现了我们的治疗目标。然而，对于一些高危患者，我们仍然需要给予更多关注。在免疫治疗的助力下，这类患者也可从一线、二线、三线乃至四线药物治疗中获益，从而获得临床缓解，同时提升其生活质量。专家简介贡铁军教授哈尔滨血液病肿瘤研究所哈尔滨血液病肿瘤研究所副所长中华医学会血液学分会常务委员中国医师协会血液科医师分会委员中国临床肿瘤学会(CSCO)骨髓瘤专家委员会副主任委员、白血病专家委员会副主任委员、淋巴瘤专家委员会委员中国抗癌协会血液肿瘤专委会常委、血液病转化专委会常委中国医院协会血液学机构分会常委国家卫健委能力建设和继续教育肿瘤学专家委员会委员《中华血液学杂志》通讯编委、《白血病淋巴瘤》编委黑龙江省医学会血液学分会副主任委员黑龙江省抗癌协会血液肿瘤专委会侯任主任委员黑龙江省医师协会淋巴瘤骨髓瘤专委会副主任委员（来源：《肿瘤瞭望–血液时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议临床结果免疫疗法细胞疗法临床1期

2025-07-04

·医学新视点

乳腺癌进展或死亡风险降低超40%，PROTAC迎来里程碑 | 2025上半年蛋白降解领域盘点

▎药明康德编者按：靶向蛋白降解剂（TPD）通过利用细胞自身的蛋白降解系统降解与疾病相关的靶蛋白。由于无需直接抑制靶蛋白的活性，这种治疗模式有望针对许多以往被认为“不可成药”的靶点，因而成为新药开发的热点领域之一。早在近10年前，这项技术刚刚起步时，药明康德就开始布局相关能力和技术，积累了丰富的成功经验，搭建起集发现、合成、分析纯化和测试等能力的一体化赋能平台。目前，该平台已成功支持超过120款TPD分子的开发，其中20余款顺利推进至临床阶段。本文将回顾2025年上半年TPD领域的最新进展。还将介绍药明康德的一体化CRDMO平台如何高效解决TPD药物开发过程中的诸多挑战，在短短12个月内完成IND申报所需的蛋白降解靶向嵌合体（PROTAC）候选药物的制备，并为首次人体临床研究提供临床试验用药。临床进展：首个PROTAC分子3期结果发布，细胞外蛋白降解疗法初步临床数据积极今年3月，辉瑞（Pfizer）和Arvinas联合公布了PROTAC药物vepdegestrant的首个关键性3期临床试验结果。在携带ESR1突变的HR阳性、HER2阴性乳腺癌患者中，vepdegestrant与活性对照相比，将患者的疾病进展或死亡风险降低超过40%（风险比低于0.60）。Arvinas和辉瑞近日已经向美国FDA递交vepdegestrant的新药申请（NDA）。此外，该公司的另一款在研PROTAC疗法ARV-102在1期临床试验中显著降低健康志愿者中枢神经系统（CNS）和外周的LRRK2蛋白水平。这一结果为后续在LRRK2相关神经退行性疾病中的进一步临床研究奠定了基础。Kymera Therapeutics公司的潜在“first-in-class”口服STAT6降解剂KT-621在1期健康受试者的临床试验中也获得积极结果。数据显示，每日一次口服KT-621，在所有高于1.5 mg剂量水平中实现了平均超过90%的血液STAT6降解；在所有≥50 mg的多剂量递增（MAD）组中，更在血液与皮肤中均达成STAT6完全降解。百时美施贵宝（Bristol Myers Squibb）在欧洲血液学协会（EHA）年会上，展示了其靶向蛋白降解平台的最新研究数据，包括其在研口服E3泛素连接酶cereblon调节剂（CELMoD）药物mezigdomide和iberdomide在多发性骨髓瘤（MM）患者中的更新临床研究结果，以及golcadomide在非霍奇金淋巴瘤（NHL）中的研究进展。此外，该公司也公布其潜在“first-in-class”的口服BCL6配体导向降解剂（LDD）BMS-986458在NHL中的初步研究结果。其中，golcadomide联合利妥昔单抗治疗复发/难治性滤泡性淋巴瘤患者展现出显著疗效，总缓解率（ORR）高达94%，完全缓解（CR）率为63%。BMS-986458的初步研究结果显示，在外周血和肿瘤组织中均观察到BCL6快速且持久的降解。从最低剂量起即观察到在弥漫性大B细胞淋巴瘤和滤泡性淋巴瘤患者中的抗肿瘤活性。在21名可评估疗效的患者中，ORR为81%（N=17），CR率为23.8%（N=5）。Biohaven公司开发的靶向蛋白降解剂BHV-1300和BHV-1400近期在早期临床试验中表现出显著降低细胞外蛋白的能力。这两款在研药物均为双特异性分子，一端与靶蛋白结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR可介导肝细胞通过内吞作用，将靶蛋白摄入细胞内并降解。临床试验数据显示，BHV-1300和BHV-1400注射入患者体内后，短短数小时内即介导了靶蛋白的快速降解，蛋白水平降幅达到70%~80%，凸显出这类药物迅速的起效速度与临床应用潜力。融资与合作：大药企持续布局分子胶药物在靶向蛋白降解领域，促进蛋白降解的双特异性分子之外，分子胶降解剂通过与单个靶蛋白或E3泛素连接酶结合，即可诱导或稳定它们之间的相互作用，从而实现蛋白降解。这一细分领域近年来不断升温。在2024年，诺华（Novartis）、渤健（Biogen）、辉瑞、武田（Takeda）、卫材（Eisai）与诺和诺德（Novo Nordisk）等多家跨国药企先后签署了单笔数额超过10亿美元的分子胶研发合作协议。进入2025年上半年，分子胶领域的布局热度依然持续。今年5月，基因泰克（Genentech）与Orionis Biosciences达成超过20亿美元的研发合作协议，致力于开发靶向难以成药靶点的小分子单价分子胶药物，用于癌症治疗。此前在今年2月，礼来（Eli Lilly and Company）也与Magnet Biomedicine公司签署一项近13亿美元的合作协议。双方合作的范围不仅涵盖基于分子胶的蛋白降解剂研发，还将探索利用分子胶促进蛋白质之间产生诱导接近和协同作用，精准靶向疾病相关组织的创新作用机制。此外，艾伯维（AbbVie）公司在1月也与Neomorph公司达成超16亿美元的分子胶蛋白降解剂研发合作。与此同时，2025年上半年，多家开发靶向蛋白降解剂的新锐公司也完成新一轮融资。具体融资及合作信息请参见下表：▲2025年上半年靶向蛋白降解领域的融资和研发合作信息（数据来源：公开资料）展望未来，靶向蛋白降解剂有着更为深远的意义。这一领域的权威，丹娜-法伯癌症研究所（Dana–Farber Cancer Institute）的Eric Fischer教授在接受Nature Medicine采访时指出，利用口服小分子药物来降解蛋白质，将改变过去受制于“可成药性”局限的研发模式，使科学家们能更自由地探索哪些靶点真正能够最大程度改变疾病的进程。期待未来有更多蛋白降解药物在临床研究中取得积极进展，造福广大患者。然而，TPD药物的广阔前景也伴随着独特的开发挑战。例如，由于分子量大、结构复杂，PROTAC类分子通常存在溶解度差和药代动力学性质不佳的问题。以下案例展示了药明康德旗下合全药业（WuXi STA）如何与合作伙伴携手，有效应对这些挑战。解决TPD药物开发痛点，加速创新疗法进入临床试验几年前，一家公司因PROTAC分子的生产难题，选择与合全药业合作，希望在14个月内完成候选药物的生产，以支持IND申请及首次人体临床试验。然而，该候选分子的初始合成路线非常复杂，需要多达24个步骤，且最终产率仅为0.3%。此外，PROTAC特定的分子结构进一步增加了产品结晶和纯化难度。同时，由于候选化合物分子量较大且水溶性低，其口服生物利用度只有0.9%。值得注意的是，在合成过程中还有三步涉及使用罕见金属钯（Pd）作为催化剂，这不仅带来潜在安全隐患，更显著提高了生产成本。针对上述问题，合全药业的工艺研发、生物催化及结晶工艺等团队协同攻关，重新设计了一条合成路线，将合成步骤从原来的24步缩减至16步，并在其中两个步骤中用生物催化剂替代了钯催化剂。为攻克结晶难题，团队采用高通量结晶筛选技术，迅速确定了符合纯度与产量要求的结晶工艺，并通过优化大幅提升了生产过程的总产率。这些改进不但极大提高了整体合成工艺的可放大性，也提升了合成效率并降低了成本。与此同时，合全药业的制剂研发团队针对药物口服生物利用度低的问题，进行了全面的生物利用度增强技术筛选，最终选定喷雾干燥制备固体分散体（SDD）技术进行制剂制备。这种技术将难溶药物以无定形状态高度分散在聚合物中，目前已成功应用于多种上市药物的制剂开发中。借助SDD技术，候选化合物药片制剂的口服生物利用度提高了约30倍，为后续临床应用奠定了坚实基础。合全药业一体化CRDMO平台的整合能力，使多个团队能够并行推进原料药与制剂开发，高效协作，加速破解PROTAC分子开发中的难题。最终，团队仅用了12个月就完成了支持IND申请所需的候选药物生产和制剂制备，顺利供应首次人体临床研究用药，比合作伙伴原定时间提前了2个月。作为赋能全球靶向蛋白降解药物开发的重要平台之一，药明康德一体化平台的能力不但涵盖PROTAC，还包括分子胶、以及多种新兴双功能性蛋白降解剂类型。例如，诱导细胞外或细胞膜蛋白进入溶酶体进行降解的溶酶体靶向嵌合体（LYTAC），将抗体与蛋白降解剂偶联产生的蛋白降解剂-抗体偶联药物（DAC），诱导靶蛋白被自噬体吞噬降解的自噬靶向嵌合小分子（AUTAC），以及靶向降解特定RNA的核糖核酸酶靶向嵌合体（RIBOTAC）等。展望未来，药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，以独特的一体化、端到端的CRDMO模式，助力靶向蛋白降解剂的开发，帮助合作伙伴将科学创新转化为惠及全球患者的变革性药物。CRDMO: H1 2025 Review of Targeted Protein Degraders Targeted protein degraders (TPDs) offer a novel therapeutic approach by leveraging the body’s own protein degradation systems to eliminate disease-associated target proteins. This strategy opens new avenues for addressing previously “undruggable” targets. Nearly a decade ago, when this technology was still in its infancy, WuXi AppTec began building relevant capabilities. Since then, the company has established a comprehensive, integrated platform encompassing discovery, synthesis, purification, analysis, and testing. To date, this platform has supported the development of more than 120 TPD molecules, with over 20 advancing to clinical stages. This article summarizes key developments in the TPD landscape during the first half of 2025. It also presents a case study demonstrating how WuXi AppTec’s integrated CRDMO platform efficiently overcomes TPD development challenges, including preparing IND-enabling materials for a proteolysis-targeting chimera (PROTAC) candidate within just 12 months for first-in-human (FIH) trials.Clinical Advances: First PROTAC Phase 3 Results and Progress in Extracellular Protein DegradersIn March 2025, Pfizer and Arvinas jointly announced top-line results from the first-ever Phase 3 clinical trial of a PROTAC therapy—vepdegestrant. In HR+, HER2- breast cancer patients with ESR1 mutations, vepdegestrant reduced the risk of disease progression or death by more than 40% compared to the active control (hazard ratio < 0.60). Arvinas and Pfizer have recently submitted a new drug application (NDA) for the drug.Arvinas' second PROTAC candidate, ARV-102, also showed promise in Phase 1 studies, achieving significant reductions in LRRK2 protein levels in both the central nervous system and peripheral tissues of healthy volunteers—laying the groundwork for future clinical trials in LRRK2-related neurodegenerative diseases.Meanwhile, Kymera Therapeutics reported positive Phase 1 results for KT-621, a potential first-in-class oral STAT6 degrader. Once-daily administration achieved over 90% average degradation of STAT6 in the blood at doses above 1.5 mg. Complete degradation in both blood and skin was observed in all multiple ascending dose (MAD) cohorts at doses ≥50 mg.Bristol Myers Squibb presented its latest research on targeted protein degradation at the European Hematology Association (EHA) 2025 Congress, highlighting progress across its protein degradation platform. This included updated clinical data on its investigational oral cereblon E3 ligase modulators (CELMoDs) mezigdomide and iberdomide in patients with multiple myeloma (MM), as well as developments in the study of golcadomide in non-Hodgkin lymphoma (NHL). Additionally, the company released initial data on BMS-986458, a potential first-in-class oral BCL6 ligand-directed degrader (LDD), in NHL.Among the findings, golcadomide in combination with rituximab demonstrated significant efficacy in patients with relapsed/refractory follicular lymphoma, with an overall response rate (ORR) of 94% and a complete response (CR) rate of 63%. Preliminary results for BMS-986458 showed rapid and sustained degradation of BCL6 in both peripheral blood and tumor tissue. Antitumor activity was observed from the lowest dose levels in patients with diffuse large B-cell lymphoma and follicular lymphoma. Among 21 evaluable patients, the ORR was 81% (N=17), with a CR rate of 23.8% (N=5).Biohaven’s BHV-1300 and BHV-1400 demonstrated rapid and robust reductions in target protein levels—achieving 70–80% decreases within hours. These molecules bind target proteins on one end and the asialoglycoprotein receptor (ASGPR) on the other, thereby facilitating internalization and degradation via endocytosis.Financing and Collaborations: Molecular Glues Attract Major DealsAlongside bifunctional degraders, molecular glues—small molecules that induce or stabilize interactions between E3 ligases and target proteins—continue to draw significant interest. In 2024, multiple major pharmaceutical companies signed R&D deals for molecular glue technologies worth over $1 billion.That momentum has carried into 2025, with several multinational pharmaceutical companies announcing collaborations focusing on molecule glue-based degraders, targeting undruggable targets in oncology, immunology, and more diseases with unmet medical needs. In addition, novel proximity-inducing mechanisms are being explored to target disease-relevant tissues with high precision. In parallel, several emerging companies in the TPD space completed new funding rounds during H1 2025. The potential of targeted protein degradation continues to expand. A recent article in Nature Medicine noted that the ability to degrade proteins with orally available small molecules is fundamentally reshaping drug discovery—liberating scientists from traditional “druggability” constraints and allowing them to focus on the targets that matter most in disease biology. As the field progresses, more TPD therapies are expected to achieve clinical milestones and ultimately bring benefits to patients worldwide.However, the promise of TPDs comes with unique development challenges. For example, due to their large molecular weight and structural complexity, PROTACs often suffer from poor solubility and suboptimal pharmacokinetics. The following case study illustrates how WuXi STA, an integral part of WuXi AppTec, collaborated with a partner to address these challenges effectively.Addressing Key Bottlenecks in TPD Drug DevelopmentSeveral years ago, a biotech company developing a PROTAC candidate faced synthetic challenges and turned to WuXi STA for support. The goal was to complete the production of drug substance and clinical trial material within 14 months to support an IND filing and FIH trial. However, the original synthesis route involved 24 steps and yielded only 0.3%. Crystallization and purification proved difficult due to the compound’s unique structure.Compounding the challenge, the candidate’s high molecular weight and poor solubility resulted in oral bioavailability of just 0.9%. Moreover, three steps in the synthesis relied on a palladium (Pd) catalyst, raising safety concerns and increasing production costs.To resolve these issues, WuXi STA’s process chemistry, biocatalysis, and crystallization teams worked in concert to redesign the synthesis route, reducing the number of steps from 24 to 16 and replacing palladium with biocatalysts in two steps. To tackle crystallization bottlenecks, high-throughput crystallization screening identified suitable conditions that met both purity and yield requirements. These changes significantly improved the scalability and efficiency of the synthetic route while reducing costs.Simultaneously, WuXi STA’s formulation team addressed the low oral bioavailability by exploring a range of enabling technologies and ultimately selected spray-dried dispersion (SDD) to prepare a solid dosage form. SDD disperses poorly soluble compounds in an amorphous state within a polymer matrix and has been successfully used in several approved drugs. With this approach, the candidate’s oral bioavailability improved by approximately 30-fold—supporting further clinical advancement.Thanks to WuXi STA’s integrated CRDMO model, API process development and formulation were advanced in parallel by multiple teams working seamlessly together. Ultimately, they delivered IND-enabling materials and clinical trial materials within just 12 months—two months ahead of schedule.As one of the industry’s leading platforms enabling targeted protein degradation, WuXi AppTec’s integrated services extend beyond PROTACs to a wide array of bifunctional modalities, including:• LYTACs (lysosome-targeting chimeras): for degrading extracellular or membrane proteins via lysosomes• DACs (degrader-antibody conjugates): combining antibodies with protein degraders• AUTACs (autophagy-targeting chimeras): small molecules inducing autophagic degradation• RIBOTACs (ribonuclease-targeting chimeras): targeting and degrading specific RNA sequencesAs targeted protein degradation continues to evolve, WuXi STA remains committed to leveraging its integrated CRDMO platform to empower the development of targeted protein degraders, helping partners translate scientific innovation into transformative medicines for patients around the world.参考资料（可上下滑动查看）[1] Induced proximity pushes beyond protein degraders, as first RIPTAC moves into the clinic. Retrieved May 15, 2025, from https://www.nature.com/articles/d41573-025-00037-7[2] Monte Rosa Therapeutics Announces Fourth Quarter 2024 Financial Results and Provides Corporate Update Including New Clinical Results from MRT-6160 and MRT-2359 Programs. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/03/20/3046104/0/en/Monte-Rosa-Therapeutics-Announces-Fourth-Quarter-2024-Financial-Results-and-Provides-Corporate-Update-Including-New-Clinical-Results-from-MRT-6160-and-MRT-2359-Programs.html[3] Magnet Biomedicine Enters into a Collaboration and License Agreement with Lilly to Discover and Develop Novel Molecular Glue Medicines. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/magnet-biomedicine-enters-into-a-collaboration-and-license-agreement-with-lilly-to-discover-and-develop-novel-molecular-glue-medicines-302387756.html[4] AbbVie and Neomorph Announce Collaboration to Develop Molecular Glue Degraders for Oncology and Immunology. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/abbvie-and-neomorph-announce-collaboration-to-develop-molecular-glue-degraders-for-oncology-and-immunology-302357741.html[5] Arvinas Presents First-in-Human Data for Investigational Oral PROTAC ARV-102 Demonstrating Blood-Brain Barrier Penetration, and Central and Peripheral LRRK2 Degradation. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/04/04/3055854/0/en/Arvinas-Presents-First-in-Human-Data-for-Investigational-Oral-PROTAC-ARV-102-Demonstrating-Blood-Brain-Barrier-Penetration-and-Central-and-Peripheral-LRRK2-Degradation.html[6] Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/03/11/3040386/0/en/Arvinas-and-Pfizer-Announce-Positive-Topline-Results-from-Phase-3-VERITAC-2-Clinical-Trial.html[7] Argobio and the Institut Pasteur launch Enodia Therapeutics: A biotech company with a new approach for Targeted protein Degradation. Retrieved May 15, 2025, from https://www.pasteur.fr/en/press-area/press-documents/argobio-and-institut-pasteur-launch-enodia-therapeutics-biotech-company-new-approach-targeted[8] Biohaven Reports Positive Degrader Data Achieving > 80% Sustained Reductions in Total IgG with Potential First-in-Class BHV-1300. Retrieved May 15, 2025, from https://ir.biohaven.com/news-releases/news-release-details/biohaven-reports-positive-degrader-data-achieving-80-sustained[9] Revolution Medicines Reports First Quarter 2025 Financial Results and Update on Corporate Progress. Retrieved May 15, 2025, from https://ir.revmed.com/node/11636[10] Photys Therapeutics Enters into Exclusive License Agreement with Polymed for Phase 1-Ready IRAK4 Degrader, Furthering its Proximity-based Pipeline and Mission. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/02/20/3029603/0/en/Photys-Therapeutics-Enters-into-Exclusive-License-Agreement-with-Polymed-for-Phase-1-Ready-IRAK4-Degrader-Furthering-its-Proximity-based-Pipeline-and-Mission.html[11] Nurix Licenses a Drug Discovery Program to Sanofi Targeting a Novel Transcription Factor for Autoimmune Diseases. Retrieved May 15, 2025, from https://ir.nurixtx.com/news-releases/news-release-details/nurix-licenses-drug-discovery-program-sanofi-targeting-novel[12] PAQ Therapeutics Announces $39 Million Series B Financing and Initiates Phase 1 Trial to Advance Novel Approach Addressing KRAS-Driven Cancers with High Unmet Need. Retrieved May 15, 2025, from https://www.prnewswire.com/news-releases/paq-therapeutics-announces-39-million-series-b-financing-and-initiates-phase-1-trial-to-advance-novel-approach-addressing-kras-driven-cancers-with-high-unmet-need-302447786.html[13] Fraser Therapeutics Secures $29 Billion Series B from J&J and 8 Others. Retrieved May 15, 2025, from http://prazertx.com/pages/board/view.php?menu_code=477&board_sid=16&data_sid=261&page_num=&skey=&sval=&category_code1=[14] TRIMTECH Therapeutics raises $31M seed funding to advance targeted protein degradation pipeline for treatment of neurodegenerative diseases. Retrieved May 15, 2025, from https://www.businesswire.com/news/home/20250305069531/en/TRIMTECH-Therapeutics-raises-%2431M-seed-funding-to-advance-targeted-protein-degradation-pipeline-for-treatment-of-neurodegenerative-diseases[15] Auron Therapeutics Announces FDA Clearance to Initiate Clinical Development of AUTX-703 and Completion of Series B Financing. Retrieved May 15, 2025, from https://www.globenewswire.com/news-release/2025/02/04/3020131/0/en/Auron-Therapeutics-Announces-FDA-Clearance-to-Initiate-Clinical-Development-of-AUTX-703-and-Completion-of-Series-B-Financing.html[16] Advancing targeted protein degraders: leveraging CMC strategies for rapid IND submission and bioavailability solutions. Retrieved May 15, 2025, from https://sta.wuxiapptec.com/wp-content/uploads/2024/10/Advancing-targeted-protein-degraders.pdf免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，传递医学新知

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D11134	-	-	DB12101

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	美国	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	日本	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	澳大利亚	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	奥地利	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	比利时	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	巴西	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	加拿大	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	捷克	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	丹麦	Alcami Corp.	2022-06-23
多发性骨髓瘤	临床3期	芬兰	Alcami Corp.	2022-06-23

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临床结果

适应症

分期

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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


NCT05199311 (phase 1/2 study, ASCO2025)	临床2期	多发性骨髓瘤	38	Carfilzomib, iberdomide, and dexamethasone (KID)	餘構醖糧餘蓋積餘築齋(艱鹹簾築製選襯顧壓鬱) = 選膚鏇製選願夢鏇範鏇夢窪蓋繭構衊壓憲網繭 (膚鹹廠窪願憲積範齋繭 ) 更多	积极	2025-05-30
NCT02773030 (CC-220-MM-001, ASCO2025)	临床1/2期	多发性骨髓瘤	18	Iberdomide, bortezomib, and dexamethasone (IberVd)	鹽糧築衊觸製觸夢夢襯(鑰範獵積憲衊窪獵膚齋) = 14 (82.4%) pts had grade (Gr) 3/4 treatment-emergent AEs (TEAEs); primarily infections (47.1%), including pneumonia (17.6%) and COVID-19 (11.8%) 鹽艱獵鑰襯選鬱膚鬱夢 (網衊製餘艱顧鑰廠窪鹽 ) 更多	积极	2025-05-30
NCT02773030 (CC-220-MM-001, EHA2025)	临床1/2期	多发性骨髓瘤	18	Iberdomide	鏇餘願憲艱膚餘壓鏇顧(遞衊築簾鬱窪選壓遞積) = 14 (82.4%) pts had grade (Gr) 3/4 treatment-emergent AEs (TEAEs); primarily infections (47.1%), including pneumonia (17.6%) and COVID-19 (11.8%) 願衊顧淵艱夢構範蓋顧 (窪窪廠鑰淵簾窪鹽膚淵 ) 更多	积极	2025-05-22
PS1784 (EHA2025)	临床2期	多发性骨髓瘤 HRCA	18	Iberdomide 1.6 mg/day + Dexamethasone	簾簾鹹齋艱鏇夢艱構網(餘遞範網夢製壓鹹衊鑰) = 網衊鏇膚膚鏇襯淵膚遞夢遞製鏇齋簾遞膚餘鹹 (觸憲選獵襯廠顧鬱窪廠 ) 更多	积极	2025-05-14
ACTRN12621001037897 (IBIS Study AMaRC 20-01, AACR2025)	临床2期	血液疾病 \| 多发性骨髓瘤	40	Iberdomide 1.6mg	齋鹽齋範淵鬱願遞鑰淵(繭簾顧選壓齋夢鏇鬱網) = 廠築糧簾範構築醖淵醖餘膚願餘鏇築範獵窪餘 (襯積鑰網鬱膚繭築鏇構, 56.0 ~ 93.1)	积极	2025-04-29
NCT04392037 (ICON, ASH2024) 人工标引	临床2期	多发性骨髓瘤	61	IberdomideCyclophosphamideDexamethasone	遞築繭餘網蓋壓夢築鹽(憲艱獵糧構獵繭積齋顧) = 簾選網衊廠壓願鬱鹽廠選鹹襯顧鹹廠築獵簾簾 (淵夢獵醖餘憲鏇顧襯壓, 14 ~ 22) 更多	积极	2024-12-08
ASH2024	N/A	多发性骨髓瘤	-	Iberdomide	鏇鬱獵鹹選繭糧襯窪製(觸膚鑰醖窪憲夢襯鹽艱) = 積衊簾製艱觸窪齋壓構觸觸簾醖餘憲觸餘遞遞 (鬱網襯製膚獵鹹壓鹹積 )	-	2024-12-07
ASH2024	N/A	阴燃多发性骨髓瘤	-	Iberdomide	艱廠壓鹹醖艱範憲憲醖(獵襯網膚顧獵醖衊鬱餘) = Six patients were diagnosed with COVID-19 while on study 餘蓋齋壓選遞鑰夢獵繭 (觸鏇遞廠鬱鑰願糧艱鏇 ) 更多	-	2024-12-07
ASH2024	N/A	阴燃多发性骨髓瘤	-	Iberdomide + Dexamethasone		-	2024-12-07
SOHO2024	N/A	多发性骨髓瘤	-	Iberdomide	齋鹽衊淵範築範壓範衊(積廠觸鬱餘鏇鑰觸憲淵) = Grade 3–4 treatment-emergent adverse events (TEAEs) occurred in 70.6% patients; most common were neutropenia (17.6%) and infections (17.6%). Occurrence of other Grade 3–4 TEAEs was low. 齋餘願願衊衊壓壓繭糧 (築齋窪膚窪蓋積艱鬱淵 )	-	2024-09-04
SOHO2024	N/A	多发性骨髓瘤	-	Mezigdomide	積淵網積遞艱醖願醖簾(遞製鹹築夢齋膚範襯願) = 範窪襯衊網築鬱艱鹹繭憲繭鑰醖選築襯觸襯淵 (繭壓襯製蓋簾憲糧築蓋, 0.03–0.13) 更多	-	2024-09-04
SOHO2024	N/A	多发性骨髓瘤	-	Iberdomide	積淵網積遞艱醖願醖簾(遞製鹹築夢齋膚範襯願) = 鑰獵範觸蓋壓襯範廠襯憲繭鑰醖選築襯觸襯淵 (繭壓襯製蓋簾憲糧築蓋, 0.03–0.13) 更多	-	2024-09-04