An Open-Label, Non-Randomized, Phase II Study to Study the Efficacy of Talquetamab (JNJ-64407564) and Lenalidomide as Post Stem Cell Transplant Maintenance in Multiple Myeloma (OPTIMMAL)

Multiple myeloma (MM) is a heterogenous plasma cell malignancy characterized by clonal proliferation of plasma cells and organ damage. Autologous transplantation with high dose chemotherapy is the standard of care in frontline treatment of eligible patients with MM.

开始日期2025-11-01

申办/合作机构

Stanford University

[+1]

NCT06965244

/ Not yet recruiting临床3期IIT

Lenalidomide vs mEthotrexate in dIfficult-to-treat cutaneouS lUpus eRythEmatosus : An Assessor-blinded Randomized Clinical Trial

Cutaneous lupus erythematosus (CLE) is a heterogeneous inflammatory autoimmune disease associated or not with systemic lupus erythematosus (SLE). Active CLE often cause pain/burning sensation and may lead to permanent visible scars and cicatricial alopecia, with psycho-social consequences/poor quality of life. First-line antimalarials (AMs) are recommended in CLE in addition to topical corticosteroids/tacrolimus with long-term response rate around 50%. Oral glucocorticosteroids (GCs) are recommended in addition to AMs for short term therapy in severe or widespread active CLE lesions. In non-responders to AMs and low-dose oral GCs, i.e., difficult-to-treat CLE, guidelines recommend the add-on of methotrexate as preferential second-line agent, with an overall efficacy of 50% in observational studies. Thalidomide has shown response rate of ≈90% in CLE in a meta-analysis of observational studies and is recommended as a second or third-line agent. However, potential severe adverse events (AEs) including teratogenicity, peripheral neuropathy and thromboembolic events limit its use.
Biological therapies including belimumab and anifrolumab, are approved only for patients with associated SLE (and not for those with isolated CLE). Their efficacy has been demonstrated as add-on therapy versus placebo but not versus a comparative drug. Moreover, efficacy of belimumab seems limited in difficult to-treat CLE and has not been assessed using validated tool, as the Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Index. Anifrolumab seems interesting in CLE associated with SLE, but its use is limited by monthly intravenous infusions, high cost and unknown long-term AEs. Moreover, its efficacy in isolated CLE has not been assessed.
Lenalidomide is a thalidomide analogue with in vitro 1000 more potent immunomodulatory properties. It is recommended as a third-line treatment in France. With more than 60 treated patients, it showed excellent and rapid efficacy with an absence of drowsiness and peripheral neuropathy with a low-dose regimen of 5 mg/day. The use of lenalidomide was to date limited by its very high cost and its indications were restricted to haematological disorders. For note, the prevention of the higher risk of thromboembolism with lenalidomide requires the daily use of low-dose aspirin.
In France, a generic of lenalidomide is now available with a monthly cost of 2 euros, allowing a broad-scale assessment of its efficacy. Finally, lenalidomide might have a better efficacy than methotrexate.
We hypothesize that lenalidomide would be more efficacious than methotrexate in difficult-to-treat CLE patients with or without associated SLE. We assume that such trial would not be supported by pharmaceutical companies.

开始日期2025-10-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

NCT06932562

/ Not yet recruiting临床3期IIT

A Randomized, Open-Label, Controlled Phase 3 Study of Comparing Daratumumab, Lenalidomide and Dexamethasone Induction Followed by Linvoseltamab Versus Continued Daratumumab, Lenalidomide, and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients

This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible).
The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.

开始日期2025-09-01

申办/合作机构

European Myeloma Network

[+1]

100 项与来那度胺相关的临床结果

登录后查看更多信息

100 项与来那度胺相关的转化医学

登录后查看更多信息

100 项与来那度胺相关的专利（医药）

登录后查看更多信息

9,387

项与来那度胺相关的文献（医药）

2025-12-31·Future Science OA

Article

作者: You, Ruxu ; Ma, Yuanyuan ; Wang, Lin ; Chen, Fen ; Zhang, Yu ; Liu, Jinyu ; Lin, Xihan

OBJECTIVE:

This study assesses the cost-effectiveness of carfilzomib plus lenalidomide and dexamethasone (KRd) versus ixazomib plus lenalidomide and dexamethasone for relapsed and refractory multiple myeloma (RRMM) in China.

METHODS:

A survival model was used to analyze health states and costs over a lifetime, with a 4-week cycle. Treatment effects on progression-free survival (PFS) and overall survival (OS) were modeled using hazard ratios (HRs) derived from the network meta-analysis (NMA). Health state utility values and disutility values for adverse events were obtained from published literature. Direct medical costs included drug costs, disease management costs, and costs associated with adverse event management. Costs and utilities were discounted by 5% annually. Both one-way and probabilistic sensitivity analyses were conducted.

RESULTS:

The carfilzomib combination was found to be cost-effective, saving $127,513.22 per additional quality-adjusted life year (QALY) gained compared to the ixazomib combination. Sensitivity analysis showed that ixazomib's price, progression state utility, and carfilzomib's price significantly affected the results. At a $40,023.27 willingness-to-pay (WTP) threshold, the carfilzomib combination has a 100% probability of being cost-effective.

CONCLUSIONS:

The study shows that, based on evidence from indirect comparisons, KRd is a cost-effective treatment option for RRMM patients in China.

2025-12-31·Hematology

RUNX1::MECOM rearrangement in myeloid neoplasm post cytotoxic therapy following sarcoma treatment: a case presentation and review of the literature

Review

作者: Kollsete Gjelberg, Hilde ; Dahl Hamnvik, Lars Henrik ; Sefland, Øystein ; Sandnes, Miriam ; Reikvam, Håkon ; Andersson Tvedt, Tor Henrik ; Ktoridou-Valen, Irini ; Brendsdal Forthun, Rakel

OBJECTIVES:

Myeloid neoplasms occurring after cytotoxic therapy (MN-pCT), previously termed therapy-related myelodysplastic neoplasia (MDS) or therapy-related acute myelogenous leukemia (AML), pose significant treatment challenges due to high resistance, poor chemotherapy tolerance, and relapse.

METHODS:

We present a 73-year-old woman with therapy-related AML following treatment for myxofibrosarcoma, characterized by the rare RUNX1::MECOM fusion resulting from a t(3;21)(q26;q22) chromosomal translocation. We also review the current literature regarding cases of this rare translocation.

RESULTS:

The patient, previously treated with chemotherapy and radiotherapy for sarcoma, was diagnosed with pancytopenia and hypoplastic bone marrow with increased blasts. Cytogenetic analysis confirmed RUNX1::MECOM fusion. Furthermore, we discuss the molecular mechanisms underlying MECOM rearrangements, specifically the role of the EVI1 oncogene. AML associated with MECOM rearrangements is associated with poor prognosis and resistance to conventional therapies. While allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potential curative treatment, the high relapse rate limits its efficacy. Recent advancements in understanding the molecular drivers of MECOM-related AML suggest potential therapeutic strategies, including hypomethylating agents and novel combinations such as lenalidomide.

CONCLUSION:

this case and literature review emphasizes the importance of long-term monitoring of cancer survivors treated with cytotoxic therapies, as well as awareness of rare translocations in MN-pCT.

2025-12-31·JOURNAL OF MEDICAL ECONOMICS

Article

作者: Li, Jia ; Mahmoudjafari, Zahra ; Masaquel, Anthony ; Parisé, Hélène ; Bercaw, Eric ; Bognar, Katalin ; Wang, Si-Tien

BACKGROUND:

Glofitamab is a T-cell engaging bispecific monoclonal antibody that was granted accelerated approval from the United States Food and Drug Administration for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after ≥2 lines of systemic therapy (3L+).

METHODS:

A budget impact model was developed for a hypothetical blended commercial/Medicare health plan with 1,000,000 members. Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine, polatuzumab vedotin + bendamustine + rituximab, rituximab + gemcitabine + oxaliplatin, tafasitamab + lenalidomide, and epcoritamab (Epcor). Total costs included those for drugs, wastage, administration, grade ≥3 adverse reactions, and all-grade cytokine release syndrome) and routine care. Market shares were based on internal projections and expert opinions. Total and per-member per-month (PMPM) net budget impacts over 3 years were calculated.

RESULTS:

Approximately nine patients were projected to be eligible for 3L + DLBCL treatment in a health plan of 1,000,000 members. The introduction of glofitamab as a treatment option resulted in estimated total and PMPM cost savings of $728,697 and -$0.0202, respectively, over 3 years. Costs were reduced across all cost categories but particularly in drug costs. Among the newer therapies, total 3-year cost per treated patient was lowest for glofitamab: $226,658 versus Tisa-cel = $564,113; Axi-cel = $540,002; Liso-cel = $516,272; and Epcor = $335,293. Across all sensitivity analyses, the inclusion of glofitamab had minimal PMPM budget impact, ranging from -$0.0256 to -$0.0108.

CONCLUSIONS:

With the lowest 3-year total cost per treated patient among the newer therapies, glofitamab being an available option in the 3L + DLBCL market is estimated to save a hypothetical 1,000,000-member health plan $728,697 in cumulative total costs and $0.0202 in PMPM costs over 3 years.

1,903

项与来那度胺相关的新闻（医药）

16 小时之前

·抗体圈

分子胶抗体偶联物：下一代ADC新模式

抗体-药物偶联物（ADCs）通过靶向递送细胞毒性药物革新了肿瘤治疗领域。然而，有效载荷多样性不足和耐药机制的出现使研究者不断探索新的有效载荷模式。分子胶-抗体偶联物（MACs）利用分子胶作为有效载荷，代表了该领域的突破性进展。通过发挥分子胶的催化、驱动特性，MACs展现出更高的疗效、更低的脱靶效应和更优的治疗指数。本文章探讨了MACs的作用机制、研究进展及其超越传统ADCs和分子胶的潜力，同时分析了开发挑战和未来方向。一. 分子胶与ADC的联用通过利用抗体的肿瘤靶向特异性，ADCs能够将细胞毒性药物精准递送至恶性组织，从而在最大化治疗效果的同时降低全身毒性。目前已有19款ADC产品获批用于20余种临床适应症。尽管ADC发展迅猛，也取得很大进展，但是当前ADC开发仍受限于有效载荷多样性不足的问题。已获批ADC的有效载荷仅涵盖两种细胞毒性机制：微管抑制和DNA损伤。这一局限凸显了探索开发具有新型作用机制替代有效载荷的迫切需求。靶向蛋白降解（TPD）已成为一种革命性的治疗策略，其通过小分子诱导效应蛋白与靶蛋白接近，从而利用内源性蛋白清除机制实现选择性蛋白消除。分子胶是一类单价小分子（通常分子量<500 Da），通过协同结合蛋白质-蛋白质相互作用（PPI）界面来促进两种蛋白的接近与结合。在TPD领域，分子胶特指能够诱导或稳定E3泛素连接酶与靶蛋白（底物）相互作用的分子胶降解剂，进而引发靶蛋白的多泛素化和随后的蛋白酶体降解。值得注意的是，分子胶具有催化性、事件驱动的作用机制，而分子胶-抗体偶联物（MACs）则由此发展成为一种新一代ADC模式（双精度靶向及催化机制）。通过将抗体靶向的精准性与分子胶的催化机制相结合，MACs展现出增强的特异性和改善的抗癌疗效潜力（图1）。图1.分子胶-抗体偶联物（MACs）的结构与优势。该图展示了分子胶负载通过连接器与抗体结合的基本结构。文中列出了传统抗体-药物偶联物（ADCs）和分子胶的局限性，并强调了MACs的优势。简化结构图显示了分子胶负载通过连接器与抗体结合的情况。2.分子胶降解剂的独特功效分子胶降解剂通过重编程哺乳动物细胞中的泛素-蛋白酶体系统(UPS)，诱导致病蛋白的多泛素化和降解。其作用机制主要体现为：这类小分子可结合E3泛素连接酶，在其表面形成全新的识别界面。这种化合物诱导的界面能够诱导通常不被UPS识别的底物蛋白(称为新底物)，进而形成E3连接酶-分子胶降解剂-新底物的稳定三元复合物。该复合物使E3连接酶与新底物空间临近，从而启动新底物的泛素化修饰及随后的蛋白酶体降解过程。分子胶降解剂因其独特的作用机制，较传统小分子药物具有多重优势。其一，其事件驱动的催化特性使得在低浓度下即可快速起效，且降解剂在完成底物降解后可循环利用。相较于需要持续占据靶点的小分子抑制剂，分子胶降解剂与靶蛋白及E3连接酶间的瞬时相互作用更能降低耐药性发生风险。其二，通过结构互补性与靶标结合的特性，使其较之靶向保守活性位点的传统小分子药物具有更高特异性。其三，能够靶向缺乏小分子结合口袋或酶活性的蛋白（如转录因子），突破传统药物"不可成药"靶点的限制。另一类与分子胶降解剂作用机制相似的TPD分子是蛋白降解靶向嵌合体(PROTACs)，虽然二者均通过重编程UPS实现蛋白降解，但存在关键区别（见图2）。分子胶降解剂和蛋白酶体靶向嵌合体（PROTACs）是基于泛素-蛋白酶体系统（UPS）的靶向蛋白质降解（TPD）技术的两种主要形式。分子胶降解剂与PROTACs的主要区别在于它们的化学结构和蛋白质招募机制。分子胶降解剂通常是小的单价分子，通过改变蛋白质的空间互补性，诱导或稳定E3连接酶与目标蛋白之间的相互作用。相比之下，PROTACs是由两个不同的配体组成的异双功能分子——一个与目标蛋白结合，另一个与E3连接酶结合——通过一个灵活的连接器相连，能够有意地将E3连接酶招募到目标蛋白上。形成稳定的三元复合物后，E3连接酶介导泛素分子转移到目标蛋白上。随后形成的多聚泛素链作为降解信号，被26S蛋白酶体识别。蛋白酶体随后将标记的蛋白质降解成小肽片段，从而实现目标蛋白的降解。3.分子胶抗体偶联物（MACs）：突破ADC与分子胶的局限性尽管ADC研发已取得重大进展，但细胞毒性药物作为有效载荷仍存在显著缺陷（图2）。具体表现为：1）需要高浓度和长时间暴露才能有效杀伤细胞；2）释放后缺乏靶向特异性；3）其毒性远强于传统化疗药物，且主要来源于天然产物，开发难度大；4）现有细胞毒性有效载荷种类有限，导致新型差异化载荷稀缺。MACs通过整合分子胶和ADC的双重优势，成功突破了两者的局限性（图2）。其创新性体现在：①抗体介导的精准递送：分子胶经抗体偶联后可精确靶向癌细胞，显著提升靶向特异性并降低脱靶效应；②药代动力学优化：抗体可增强分子胶的细胞内摄取并延长其半衰期；③治疗指数提升：相较游离分子胶，MACs能以更低系统浓度实现等效降解活性，从而拓宽治疗窗口、改善耐受性并减少副作用；④双精度靶向：通过协同分子胶的底物选择性和抗体的抗原特异性，实现对肿瘤细胞的双重精准靶向，同时最大限度降低脱靶效应。这些突破性优势使MACs成为极具前景的新一代治疗模式。图2.分子胶降解剂与PROTACs的比较。(A)分子胶降解剂和PROTACs介导的蛋白质降解过程。这两种降解剂都能将特定的E3连接酶与目标蛋白（底物或POI)靠近，形成三元复合体，并依次将泛素分子附着到目标蛋白上，最终导致其通过蛋白酶体途径降解。(B)分子胶降解剂与PROTACs的区别。4.MACs的作用机制MACs的作用机制在初始单抗介导过程中与传统ADCs相似，但在细胞杀伤机制上存在本质差异。其作用流程可分为以下关键步骤（如图3所示）：1）靶向结合阶段单克隆抗体特异性识别癌细胞表面抗原，通过受体介导的内吞作用完成内化。2）胞内释放阶段形成内吞体并转运至溶酶体，溶酶体降解作用释放分子胶至细胞质。3）蛋白降解阶段（核心差异点）分子胶诱导特定底物与E3泛素连接酶空间接近，形成"E3-分子胶-底物"三元复合物，通过26S蛋白酶体系统完成底物泛素化修饰及降解。4）细胞死亡效应靶蛋白的持续性降解，最终触发癌细胞程序性死亡。图3.MAC的作用机制。MAC的作用机制包括几个关键步骤：(i)结合：单克隆抗体（mAb）与肿瘤细胞表面的抗原（目标1）结合。（ii）内化：MAC-抗原复合物被囊泡包裹，并通过内吞作用进入细胞内部。（iii）溶解：MAC-抗原复合物在溶酶体中被分解。（iv）负载释放：分子胶从MAC中释放，进入细胞质。(v)三元复合物形成：分子胶促进E3泛素连接酶与底物（目标2）之间的相互作用，形成E3连接酶-分子胶-底物复合物。（vi）泛素化：一旦三元复合物形成，E3连接酶将泛素分子转移到底物上。（vii）降解：泛素标记的底物被26S蛋白酶体识别并降解为小肽。（viii）分子胶的循环利用：底物降解后，分子胶被释放，可以参与进一步的泛素化过程，成为催化降解剂。机制优势：相较于传统ADCs的细胞毒性杀伤，MACs有以下优势：1）催化性蛋白降解实现信号通路阻断2）多轮次降解作用放大药效3）避免化疗药物常见的耐药机制5.分子胶降解剂-抗体偶联物临床进展5.1 ORM-5029ORM-5029由Orum Therapeutics开发，是一种首创新药分子胶降解剂-抗体偶联物，已进入临床试验。目前，该药物正在接受针对HER2阳性晚期实体瘤患者的I期剂量递增试验（NCT05511844）的评估。ORM-5029由三大核心组分构成：1. 靶向元件：抗HER2抗体帕妥珠单抗（pertuzumab）2. 效应元件：G1/S期转换蛋白1（GSPT1）分子胶降解剂SMol0063. 连接系统：缬氨酸-瓜氨酸（Val-Cit）-PABC可切割型连接子，其DAR为4（图4）图4.MACs的结构。每个结合物中，分子胶以黑色表示，连接子以绿色显示。粉红色的液滴带有细波线，表示额外的连接子-分子胶分子。有效载荷SMol006是通过对分子胶降解剂CC-885进行系统优化而开发的。其关键结构改造包括：将3-氯-4-甲基苯基团中的甲基替换为2-(2-(甲氨基)乙氧基)乙基。这一结构修饰通过以下方式显著提升了药物性能：1）溶解性优化：引入极性基团增强水溶性2）分子柔性改善：提高分子构象灵活性3）偶联位点构建：为后续连接化学提供反应位点体外实验结果显示，ORM-5029在14种HER2阳性乳腺癌细胞系中均表现出强劲的抗肿瘤活性，其IC50范围为0.3-14.4 nM。临床前研究中，该药物显示出优于现有HER2靶向ADC药物T-DXd的效力（表现为更低的IC50值）。5.2 ORM-6151 (BMS-986497)ORM-6151/BMS-986497核心组分构成:1. 结构设计有效载荷：采用GSPT1降解剂SMol006 靶向元件：抗CD33单抗连接系统：β-葡萄糖醛酸连接子偶联比：DAR=4（见图3） 2. 开发进展原研企业：Orum Therapeutics 权益转让：2023年被百时美施贵宝（Bristol Myers Squibb, BMS）收购商品命名：BMS-986497（BMS研发代号）3. 临床开发里程碑2024年获FDA批准开展I期临床试验适应症：复发/难治性急性髓系白血病（AML）或骨髓增生异常综合征（MDS）临床试验编号：NCT06419634 该药物延续了SMol006的双重优势：高效诱导GSPT1蛋白降解和显著降低对正常造血干细胞的毒性。 5.3 TE-1146抗CD38抗体达雷妥尤单抗和来那度胺均为治疗多发性骨髓瘤（MM）的药物选择。然而，MM至今仍无法治愈，几乎所有患者最终都会复发。为解决这一问题，Immunwork公司开发了TE-1146，这是一种分子胶降解剂-抗体偶联物。这种创新疗法将重新配置的daratumumab与通过多臂连接子在C末端进行位点特异性偶联的来那度胺相结合，DAR为6（图4）。TE-1146是通过Immunwork High DAR平台制备的，该平台专为设计药物抗体比（DAR）>4的均质抗体偶联药物（ADC）而开发。该平台采用两项创新结构：（1）通过计算机设计、含有半胱氨酸的锌离子结合肽（ACPGHA），可延伸至单抗每条重链的C末端；（2）含马来酰亚胺的多臂肽核心连接子，能结合三个药物分子形成药物簇。偶联过程通过硫醇-马来酰亚胺反应，将两个药物簇连接至结构优化的单抗上。体外研究证实，TE-1146具有剂量依赖性细胞毒性：其对CD38阳性多发性骨髓瘤细胞系H929和MM.1S的半效浓度（EC50）约为0.45 μM，而对CD38阴性的U266细胞无显著作用。相比之下，即便浓度超过20 μM，达雷妥尤单抗单药仍无法诱导细胞死亡——因其作用机制依赖于自然杀伤细胞等免疫细胞发挥作用。来那度胺单药或与达雷妥尤单抗以6:1摩尔比联用时，在>10 μM浓度下仅显示微弱细胞毒性，这可能与细胞摄取效率有限有关。TE-1146的效力较来那度胺单药或其与达雷妥尤单抗联用方案强100倍以上。在体内实验中，TE-1146在H929 NOD-SCID小鼠移植瘤模型中展现出显著疗效。单次给药20 nmol/kg即可完全清除肿瘤，而同等剂量的达雷妥尤单抗仅能中度抑制肿瘤生长。达雷妥尤单抗与来那度胺联用方案在前两周可延缓肿瘤生长，但即便提高剂量（40或80 nmol/kg）也无法维持后续抑瘤效果。这些结果凸显了TE-1146在体外和体内模型中均具有卓越的抗肿瘤功效，这归因于其能高效递送并将来那度胺内化至骨髓瘤细胞内，预示该药物在多发性骨髓瘤治疗中具有广阔前景。5.4 c-MYC降解的MACsc-MYC是一种转录因子，它在超过一半的人类癌症中频繁过表达或激活，是一个极具吸引力但极具挑战性的治疗目标。尽管c-MYC在致癌方面具有重要意义，但由于其固有的无序性、缺乏酶活性以及没有明确的配体结合位点，开发针对c-MYC的有效小分子抑制剂一直受到阻碍，传统上认为它是‘难以成药。近日，苏州开拓药业/医克生物通过设计新型分子胶降解剂取得重大突破，该系列化合物能引导c-MYC蛋白与E3泛素连接酶CRBN结合，最终实现c-MYC的降解。从结构上看，这些沙利度胺类似物具有以下特征：(1) 保守的戊二酰亚胺环（负责与CRBN相互作用）；(2) 经过修饰的邻苯二甲酰环（可与c-MYC形成特异性结合界面）。通过医克生物TMALIN平台，优选降解剂D-1、D-4和D-10经可裂解三肽连接子与抗前列腺特异性膜抗原（PSMA）单抗偶联，实现DAR为2（图4）。PSMA作为ADC靶点具有显著优势，因其不会脱落进入循环系统，且能在抗体结合后高效内化。体外实验显示，与未偶联的降解剂（D-4、D-1和D-10）相比，偶联分子MAC-001、MAC-002和MAC-003对PSMA阴性的人白血病HL60U细胞及正常外周血单个核细胞（PBMCs）的抗增殖活性有所降低。然而，这些偶联物在PSMA阳性的前列腺癌22RV1和VCap细胞中表现出显著增强的细胞毒性，表明抗体偶联可提高分子胶降解剂的选择性杀伤效应。研究人员进一步在过表达PSMA的22RV1皮下移植瘤小鼠模型中评估了这些偶联物的治疗潜力。每周两次静脉注射MAC-002（剂量为5和10 mg/kg，持续21天）可显著抑制肿瘤生长，抑制率分别达到31.8%和72%。这些令人鼓舞的结果凸显了c-MYC降解型MAC药物作为治疗c-MYC驱动型肿瘤的新型策略的应用前景。5.5 乐高MAC韩国LegoChem Biosciences公司近期公开了一种基于免疫调节药物（IMiDs）化学骨架开发分子胶降解剂的新方法。这些分子胶降解剂通过与单抗偶联，可生成DAR为2的均质化、位点特异性MACs（图4）。该偶联过程采用LegoChem专有技术，包含四个关键步骤：（1）构建重组质粒，用于表达在每条轻链C端含有半胱氨酸肽段（CVIM）的抗体；（2）通过在各轻链C端添加异戊二烯基团实现抗体异戊烯化修饰；（3）采用带有氨基氧基团的β-葡萄糖醛酸连接子对分子胶化合物进行修饰；（4）通过肟连接反应实现抗体与连接子-载荷的位点特异性偶联。体外实验分析表明，与未偶联的分子胶降解剂相比，这些MACs展现出显著增强的抗增殖活性。以HCC827细胞系为例，未偶联分子胶的半数抑制浓度（IC50）为10.2 nM，而经抗EGFR抗体偶联的MACs的IC50达到0.09 nM，药效提升了110倍。这些发现凸显了MACs作为靶向癌症治疗强效策略的应用潜力。5.6 Affibody-CR8偶联物亲和体（Affibodies）是一类小分子（6.5 kDa）非抗体单链蛋白支架，能够特异性结合某些肿瘤过表达的受体。由于其结构简单，亲和体易于修饰以实现有效载荷的偶联。因此，部分亲和体已被选作靶向载体，用于构建亲和体-药物偶联物（affibody-drug conjugate），实现靶向给药。研究人员构建了一种新型亲和体-分子胶降解剂偶联纳米制剂，该制剂由以下组分构成：(1) 经修饰的抗HER2亲和体（ZHER2:342-36FSY-Cys；FSY为氟磺酰-L-酪氨酸）；(2) 细胞周期蛋白K降解剂CR8；(3) 含二硫键的可裂解连接子（图4）。该亲和体-CR8偶联物可在磷酸盐缓冲液（PBS）中自组装形成纳米制剂。在细胞实验中，由于亲和体通过HER2内吞作用介导的内化效应，亲和体-CR8偶联物展现出比游离CR8更强的细胞周期蛋白K降解能力。值得注意的是，游离CR8对所有测试癌细胞均具有强细胞毒性（IC50值在纳摩尔范围内），而亲和体-CR8偶联物则表现出差异化的细胞毒性：其对HER2阳性SKOV-3细胞的IC50为338.20 nM，对HER2阴性MDA-MB-453细胞的IC50则高达1.98 μM。在安全性评估中，小鼠每3天通过尾静脉注射接受CR8当量剂量5 mg/kg的亲和体-CR8偶联物，30天内未观察到不良反应。与对照组相比，实验组小鼠的体重、血液学参数、肝肾功能及器官组织学均未见显著变化，证实了该偶联物良好的体内安全性。6.分子胶稳定剂-抗体结合物能够以惊人效率促使两种蛋白质结合并产生功能效应的小分子单价化合物被定义为分子胶。这类化合物不仅能降解靶蛋白，还可稳定或破坏靶蛋白结构。例如著名分子胶稳定剂紫杉醇（Taxol®）可增强α-微管蛋白与β-微管蛋白的结合，从而阻止微管解聚并诱导有丝分裂停滞。尽管目前用作有效载荷的分子胶多为降解剂，但分子胶稳定剂同样具备载药潜力。最新研究表明，基于稳定剂的MACs为蛋白质功能调控提供了新思路，进一步拓展了MACs在癌症治疗等领域的应用前景。6.1 磷酸抗原（pAg）-抗体结合物磷酸化抗原（pAgs）是细胞代谢过程中产生的磷酸化中间体。在癌细胞中，代谢通路的失调会导致pAgs的异常积累，从而增强这些细胞被γδ T细胞识别和清除的敏感性。最新研究发现，细胞内pAgs可作为分子胶稳定剂发挥作用。例如，它们能促进跨膜蛋白BTN3A1（嗜乳脂蛋白3A1）和BTN2A1（嗜乳脂蛋白2A1）的胞内结构域形成稳定的异源二聚体。这种相互作用会进一步促使二聚体的胞外结构域与γδ T细胞受体结合，从而激活γδ T细胞对肿瘤细胞的靶向清除功能。Byondis BV公司最新开发了一系列以磷酸化抗原（pAgs）为有效载荷的MACs。这些pAg载荷通过可裂解连接子与多种靶向抗体偶联，包括利妥昔单抗（抗CD20）、曲妥珠单抗（抗HER2）、抗CD123抗体及抗5T4抗体，DAR为2。以利妥昔单抗与连接子-pAg复合物XS58形成的MAC为例进行评估（图4）。在活性测试中，将CD20阳性的Raji细胞分别与裸利妥昔单抗或利妥昔单抗-XS58共孵育过夜后，再与含γδ T细胞的外周血单个核细胞（PBMCs）共培养6小时。结果显示，经利妥昔单抗-XS58预处理的Raji细胞能显著提升γδ T细胞的干扰素（IFN）-γ和CD107a分泌水平，充分体现了基于pAg的MACs的强大免疫刺激效应。该策略彰显了pAg偶联抗体在利用γδ T细胞免疫机制治疗癌症方面的巨大潜力。6.2 CD184-FK506由Ambrx公司研发的CD184-FK506是一种靶向CD184（又称CXCR4）的新型治疗性偶联物。其有效载荷FK506是一种天然来源的免疫抑制剂，同时被鉴定为分子胶稳定剂。从作用机制来看，FK506可与FK506结合蛋白12（FKBP12）结合形成复合物，该复合物能协同紧密地结合钙调磷酸酶（calcineurin），从而抑制其活性。FKBP12-FK506-钙调磷酸酶三元复合物的晶体结构证实：单独的FK506或FKBP12均无法以显著亲和力结合钙调磷酸酶。Ambrx的技术方案是将FK506与CD184特异性靶向分子偶联，但具体的连接子设计、偶联位点及DAR值等细节尚未公开。7.总结和未来展望7.1挑战分子胶作为治疗药物，其临床应用历史远早于作用机制的阐明时间。近年来，用于癌症治疗的MACs研发取得重大进展（表1）。通过将抗体的肿瘤靶向能力与具有新型作用机制的有效载荷相结合，MACs已成为药物化学领域最具前景的突破之一。目前，MACs已超越概念验证阶段，其中两个候选药物（ORM-5029和ORM-6151）正处于I期临床试验阶段。值得注意的是，与靶向相同抗原的现有ADC药物相比，二者均展现出独特优势：具体而言，ORM-5029在T-DM1耐药和HER2低表达的移植瘤模型中均表现出强效抗肿瘤活性，从而突破了当前HER2靶向ADC药物的关键局限；而ORM-6151相较于Mylotarg（吉妥珠单抗奥唑米星），对CD33阳性细胞展现出更高的选择性，有望提供更优的临床安全性和更宽的治疗窗。表1.本文中分子胶-抗体结合物的总结备注：黄色椭圆处为分子胶化学结构中的连接位点分子胶降解剂领域目前正处于快速发展阶段，不仅靶向多种癌症，还涉及非肿瘤性疾病领域，包括神经系统疾病、自身免疫性疾病和血液系统疾病等。鉴于搭载非化疗类有效载荷的ADC药物已在炎症性疾病、免疫紊乱、视网膜病变及细菌感染等领域展现出治疗潜力，预计MACs通过采用非肿瘤靶向的分子胶降解剂，同样有望拓展其治疗范围。尽管MACs前景广阔，但其开发仍面临诸多挑战。首要限制在于分子胶降解剂的稀缺性——这类化合物历史上多通过偶然发现获得。由于需要独特地重塑蛋白质表面结构并与两种蛋白形成三元复合物，分子胶的理性设计本身极具挑战性。此外，作为MACs的有效载荷，分子胶必须满足严格标准：既需具备可供化学修饰的活性基团，又需确保修饰不影响其生物功能。这些限制条件大幅缩小了候选分子的选择范围。更重要的是，MACs作为多组分复合体系，其药物抗体比、连接子稳定性和偶联方法等参数都会显著影响药效与毒性。另一个关键考量是：分子胶会永久性降解靶蛋白，虽然这种作用机制可能非常有效，但也带来风险——一旦出现副作用将难以逆转。鉴于传统ADCs和分子胶均已出现耐药现象，MACs也可能面临类似挑战。由于MACs通过双重靶向并调控多个细胞内进程发挥作用，其耐药机制可能包括：靶抗原或新底物的下调、溶酶体蛋白水解活性受损、药物外排转运蛋白上调，以及E3连接酶表达异常等多种途径。7.2 未来展望近年来，结构生物学、人工智能（AI）与机器学习（ML）的融合彻底改变了分子胶及其偶联物的开发模式（图5）。在靶点识别阶段，AlphaFold2可实现全蛋白质组范围内易降解蛋白的预测。几何深度学习等先进ML方法能精准预测三维蛋白复合体结构及蛋白-配体相互作用，这对理解分子胶介导的靶标结合机制至关重要。此外，生成式AI已助力构建分子胶化合物库，基于ML的定量结构-性质关系（QSPR）模型则可预测靶向蛋白降解（TPD）化合物的吸收、分布、代谢和排泄（ADME）特性。这些方法的整合实现了降解剂分子的系统化设计与优化。展望未来，AI推理模型或能全面分析抗体与分子胶的靶点及组织选择性，从而预测MACs的最佳组合方案与适应症。虽然此类模型尚未完全实现，但其开发至关重要，未来还可拓展至AI辅助的ADC设计领域。图5.分子胶-抗体结合物（MACs）的人工智能（AI）/机器学习（ML）驱动开发路线图。主要阶段包括：(1)利用AlphaFold预测蛋白质结构，以识别新的易降解目标。(2)通过几何深度学习进行复杂预测，结合基于扩散的生成式AI设计降解剂，采用降解效力评分和定量结构-性质关系（QSPR）模型来预测吸收、分布、代谢和排泄（ADME）特性。(3)通过MAC设计和优化，确定分子胶、连接子和抗体的最佳组合。AI/ML平台通过全面分析目标和组织的选择性，预测合适的临床应用，并确定最佳的分子胶-连接子-抗体组合。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！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。

抗体药物偶联物蛋白降解靶向嵌合体

2025-06-29

·GlobeNewswire-Health Care

Sarclisa recommended for EU approval by the CHMP to treat transplant-eligible newly diagnosed multiple myeloma Recommendation based on GMMG-HD7 phase 3 study demonstrating that Sarclisa with VRd induction treatment significantly improved MRD negativity benefit and prolonged PFS compared to VRd alone If approved, it would represent the fourth indication in the EU and second in the front-line setting globally June 23, 2025. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the induction treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant. A final decision is expected in the coming months. Olivier Nataf Global Head, Oncology “The CHMP’s recommendation represents significant progress toward our ambition for Sarclisa, addressing unmet patient needs in multiple myeloma care and making a meaningful difference in treatment outcomes at every stage of the disease across regions. If approved, this regimen would represent a new, important induction option for transplant-eligible patients, with the potential to improve long-term outcomes and deepen responses at a critical juncture in treatment.” The positive CHMP opinion is based on part one results from the two-part, double-randomized, German-speaking Myeloma Multicenter Group (GMMG)-HD7 study (clinical study identifier: NCT03617731), presented at the 2024 American Society of Hematology Annual Meeting & Exposition and published in the Journal of Clinical Oncology. GMMG-HD7 is the first phase 3 study to demonstrate a deep and rapid response with an anti-CD38-based induction regimen in transplant-eligible (TE) NDMM patients, with a higher proportion of patients with minimal residual disease (MRD) negativity benefit post-induction, alongside a significant progression-free survival (PFS) benefit from first randomization, regardless of maintenance therapy and without consolidation. Additionally, the data showed the highest post-induction and post-transplant MRD negativity rates of any CD38 monoclonal antibody using VRd as a backbone in TE NDMM. The results are part of the growing body of clinical evidence supporting the use of Sarclisa in the front-line setting and reinforce the potential of Sarclisa-VRd when used prior to transplant. Sarclisa is currently approved in three indications in the EU, across different lines of therapy in adult patients with relapsed and/or refractory (R/R) MM and with NDMM who are not eligible for transplant. GMMG-HD7 is an investigational pivotal, randomized, open-label, multicenter, two-part phase 3 study evaluating Sarclisa in combination with VRd, also referred to as RVd (lenalidomide, bortezomib, and dexamethasone), versus VRd induction followed by post-transplant re-randomization to Sarclisa plus lenalidomide versus lenalidomide maintenance in TE NDMM patients. The GMMG-initiated study is being conducted in close collaboration with Sanofi based on jointly defined research. Sanofi provided financial support to GMMG for this study. In December 2021, Sanofi and GMMG shared results from part one, which met the primary endpoint of MRD negativity after induction therapy and before transplant in NDMM patients. The study enrolled 662 patients with TE NDMM across 67 sites in Germany. In the first part of the study, all participants were equally randomized to receive three 42-day cycles of VRd in both arms of the study, while Sarclisa was added to only one study arm. In the second part of the study, patients were re-randomized post-transplant to receive Sarclisa plus lenalidomide or lenalidomide alone as maintenance therapy. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction period. The GMMG-HD7 protocol defined two primary endpoints: MRD negativity following induction therapy in the first part of the study, and PFS after the second randomization post-transplant in the second part, where Sarclisa was added to lenalidomide maintenance. The latter endpoint is expected to be available at a later time. The key secondary endpoint for the first part of the study was PFS from first randomization. Additional secondary endpoints included rates of complete response after induction, and intensification, overall survival, and safety. MRD negativity was assessed by next-generation flow cytometry (sensitivity of 1x10-5) after induction. In the latest results, PFS for both arms, regardless of maintenance therapy, were measured from the first randomization. Sarclisa (isatuximab) is approved in more than 50 countries, including in the US, EU, Japan, and China, across multiple treatment lines for MM. Based on the ICARIA-MM phase 3 study, Sarclisa is approved in the US, EU and Japan in combination with pomalidomide and dexamethasone for the treatment of patients with R/R MM who have received ≥two prior therapies, including lenalidomide and a proteasome inhibitor and have relapsed on the last therapy; this combination is also approved in China for patients who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. Based on the IKEMA phase 3 study, Sarclisa is also approved in more than 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with R/R MM who have received one to three prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, EU, UK, and China, Sarclisa is approved in combination with VRd as a front-line treatment option in transplant-ineligible NDMM patients, based on the IMROZ phase 3 study. In Japan, Sarclisa is approved in combination with VRd as a front-line treatment option regardless of transplant eligibility. At Sanofi, we are building on a long-standing commitment to oncology as we continue to chase the miracles of science to improve the lives of those living with cancer. We are committed to transforming cancer care by developing innovative, first and best-in-class immunological and targeted therapies for rare and difficult-to-treat cancers with high unmet need. GMMG is the largest study group focusing on MM in Germany, with headquarters based in Heidelberg. Within the last 20+ years, the GMMG study group has performed numerous studies including five randomized, multicenter phase 3 studies with 4,000 patients enrolled from about 90 participating and cotreating centers throughout Germany. The overall goal of GMMG is to generate improved therapies for myeloma patients through the development and testing of novel and personalized, genome- and signaling driven treatment strategies. The GMMG has set itself the goal of achieving further approvals for effective antibody-based drug combinations for the first-line treatment of myeloma patients, in which antibody-based treatment regimens have been integrated into seven GMMG study concepts (CONCEPT, DANTE, DADA, HD6, HD7, HD8, HD9 and HD10). Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and delivering compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. The content above comes from the network. if any infringement, please contact us to modify.

临床3期临床结果上市批准ASH会议免疫疗法

2025-06-28

·药明康德

使六成患者获完全缓解的免疫组合疗法；2-4天快速起效的干眼症多肽疗法…… | TIDES周报

▎药明康德近期，全球多肽和寡核苷酸（TIDES）领域迎来系列进展。Enterome公司基于肿瘤肽的免疫疗法EO2463联用来那度胺和利妥昔单抗治疗惰性非霍奇金淋巴瘤（NHL），在一项2期临床试验中的完全缓解（CR）率达60%。用于治疗代谢功能障碍相关性脂肪性肝炎（MASH）和肥胖症的胰高血糖素样肽-1（GLP-1）/胰高血糖素双重受体激动剂pemvidutide达2b期临床试验主要终点。在研环肽疗法certepetide联合标准化疗治疗转移性胰腺导管腺癌（mPDAC），患者的无进展生存期和客观缓解率（ORR）都获得了有临床意义的改善。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。EO2463：公布2期联合治疗试验的中期数据Enterome公司公布了其基于肿瘤肽的免疫疗法EO2463与来那度胺和利妥昔单抗联用治疗惰性NHL的积极2期临床结果。EO2463由4种模拟B细胞肿瘤相关抗原CD20、CD22、CD37和CD268（BAFF受体）的多肽以及辅助性的UCP2肽组成，能够激活抗肿瘤免疫反应，清除癌变B细胞。此次公布的结果显示，EO2463联合来那度胺和利妥昔单抗治疗后，60%（12/20）的患者达到了CR。该组合疗法在滤泡性淋巴瘤和边缘区淋巴瘤患者中耐受性良好。此外，该研究中观察到的CR率高于历史数据中来那度胺联用利妥昔单抗治疗所预期的水平。Certepetide：公布2b期联合治疗试验数据Lisata Therapeutics公司与澳大利亚胃肠试验组（AGITG）、悉尼大学NHMRC临床试验中心公布了2b期临床试验ASCEND的初步结果。该试验评估了Lisata公司的在研环肽疗法certepetide联合标准治疗化疗用于治疗转移性胰腺导管腺癌患者的效果。Certepetide旨在激活一种肿瘤特异性的转运系统，使与之联合使用的全身性抗癌药物能够更有效地穿透肿瘤并在肿瘤内蓄积。此外，certepetide还被证明可以调节肿瘤微环境，使肿瘤对免疫疗法更加敏感。该研究包括两个队列，队列A的患者在吉西他滨输注结束后、白蛋白紫杉醇输注开始前，静脉推注certepetide 3.2 mg/kg。队列B的患者在队列A治疗方案的基础上，在首次给药4小时后追加一次certepetide或安慰剂。此前公布的队列A的结果显示，患者的总生存期呈现出积极趋势，并且有4例患者达到CR，而安慰剂组未观察到任何CR病例。此次公布的队列B的初步数据显示，certepetide组的6个月无进展生存率为60.8%，安慰剂组为25%；两组的中位无进展生存期分别为7.5个月和4.7个月；ORR分别为45.2%和19%；中位总生存期分别为10.32个月和9.23个月。队列A和队列B的数据比较表明，在标准化疗中加入两剂certepetide（队列B方案）使mPDAC患者的无进展生存期和ORR都获得了有临床意义的改善。Pemvidutide：公布2b期临床试验数据Altimmune公司公布了pemvidutide治疗MASLD的2b期试验的积极结果。Pemvidutide是一种GLP-1/胰高血糖素双重受体激动剂，目前正在开发用于治疗MASH和肥胖症。该研究中，212名经活检证实的MASH和纤维化F2/F3期伴或不伴糖尿病的受试者按1：2：2的比例被随机分配接受pemvidutide（1.2 mg或1.8 mg）或安慰剂，持续24周。此次公布的结果显示，在意向治疗（ITT）人群分析中，试验达到了其主要终点。在24周时，pemvidutide高剂量组患者中有59.1%达到了MASH缓解，且未出现纤维化的恶化；34.5%的受试者出现了纤维化改善，且没有发生MASH的加重。基于人工智能（AI）的补充分析表明，接受pemvidutide治疗24周后，患者的肝纤维化改善具有统计学意义。此外，pemvidutide高剂量组患者在24周时的平均减重幅度达到6.2%，且体重仍在持续下降，尚未出现平台期。安全性方面，pemvidutide表现出潜在“best-in-class”的耐受性，因不良事件而停药的比例低于1%。Vezocolmitide（ST-100）：公布3期临床试验的初步数据Stuart Therapeutics公司公布了其3期临床试验的初步结果，该试验评估了ST-100滴眼液治疗干眼症（DED）的疗效。ST-100是一种胶原模拟肽类药物，其独特机制可通过修复眼部受损的胶原蛋白来恢复眼表稳态，从而减轻DED的影响。此次公布的结果显示，ST-100治疗起效迅速，在治疗2-4天内就能缓解患者的体征和症状。其中，ST-100治疗一周后荧光素染色评分（用于量化眼表上皮细胞损伤程度）的改善幅度超过了现有已批准的DED治疗药物/产品的公开报告数据。该研究结果将有助于指导ST-100的第二项3期研究的设计。Salanersen（BIIB115/ION306）：公布1期临床试验的中期数据渤健（Biogen）公布了其在研反义寡核苷酸（ASO）疗法salanersen（BIIB115/ION306）用于治疗脊髓性肌萎缩症（SMA）的一项1期临床试验的积极结果。Salanersen最初由Ionis Pharmaceuticals发现，渤健之前从Ionis Pharmaceuticals获得了salanersen的全球开发、生产及商业化权利。该药物与渤健已获批的ASO疗法Spinraza（nusinersen）具有相同的作用机制，但在设计上追求更高效力，并有望实现每年仅需一次给药。在此次中期分析中，研究对象为一组既往接受过基因治疗但临床状态仍不理想的SMA患儿。结果显示，无论是40 mg还是80 mg剂量，salanersen均表现出良好的耐受性，并可显著降低神经退行性标志物神经丝轻链（NfL）的水平。在基线NfL浓度较高的患者中，治疗6个月后平均NfL下降幅度达70%，这一效果可持续维持至一年。除了安全性和生物标志物数据外，研究还对部分随访时间达到一年的患儿（n=8，年龄2至12岁）进行了初步临床结局评估，结果同样令人鼓舞。半数患者（4人）达成了此前无法独立完成或需他人协助完成的世界卫生组织（WHO）运动发育里程碑，如独立行走、爬行、站立或坐起。基于这一积极成果，渤健正与监管机构沟通，计划推进salanersen进入注册性临床研究阶段，进一步拓展该公司在SMA治疗领域的布局。BW-40202：1期临床试验完成首例受试者给药舶望制药宣布，其在研小干扰RNA（siRNA）药物BW-40202的1期临床试验已完成首例健康受试者给药，该里程碑在澳大利亚临床研究中心达成。此外，BW-40202已获得中国国家药品监督管理局（NMPA）的IND批准，将在中国临床研究中心同步推进。BW-40202是一种靶向肝脏中补体因子B（CFB）mRNA的siRNA药物，用于治疗补体介导疾病。该药物通过抑制CFB mRNA的表达来降低血清CFB蛋白水平，并抑制补体替代途径（CAP）活性。在临床前研究中，BW-40202表现出优异的纯度和稳定性，能够显著降低血清CFB蛋白水平，有效抑制CAP活性，并具有长效性和良好的安全性。参考资料（可上下滑动查看）[1] RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY OF MONTHLY MARITIDE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS. Retrieved June 23, 2025, from https://www.prnewswire.com/news-releases/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions-302487811.html[2] Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html[3] Verdiva Bio to Present New Data Highlighting Once-Weekly Potential of Its Investigational Oral Obesity Candidates at the ADA 85th Scientific Sessions. Retrieved June 21, 2025, from https://www.businesswire.com/news/home/20250620108098/en/Verdiva-Bio-to-Present-New-Data-Highlighting-Once-Weekly-Potential-of-Its-Investigational-Oral-Obesity-Candidates-at-the-ADA-85th-Scientific-Sessions[4] Enterome presents positive Phase 2 interim results in relapsed/refractory indolent non-Hodgkin lymphoma after EO2463 OncoMimics™ immunotherapy treatment at ICML. Retrieved June 27, 2025, from https://www.globenewswire.com/news-release/2025/06/23/3103112/0/en/Enterome-presents-positive-Phase-2-interim-results-in-relapsed-refractory-indolent-non-Hodgkin-lymphoma-after-EO2463-OncoMimics-immunotherapy-treatment-at-ICML.html[5] Novo Nordisk: Higher dose of Wegovy® provided average weight loss of 21% in people with obesity – with a third achieving 25% or more – according to data presented at ADA. Retrieved June 27, 2025, from https://www.globenewswire.com/news-release/2025/06/20/3102978/0/en/Novo-Nordisk-Higher-dose-of-Wegovy-provided-average-weight-loss-of-21-in-people-with-obesity-with-a-third-achieving-25-or-more-according-to-data-presented-at-ADA.html[6] Semaglutide Increases Walking Capacity in Patients with Peripheral Artery Disease and Type 2 Diabetes. Retrieved June 27, 2025, from https://www.prnewswire.com/news-releases/semaglutide-increases-walking-capacity-in-patients-with-peripheral-artery-disease-and-type-2-diabetes-302486241.html[7] Oral Semaglutide Significantly Improves Cardiovascular Outcomes in Individuals with Type 2 Diabetes. Retrieved June 27, 2025, from https://www.prnewswire.com/news-releases/oral-semaglutide-significantly-improves-cardiovascular-outcomes-in-individuals-with-type-2-diabetes-302487712.html[8] 甘李药业双周GLP-1RA博凡格鲁肽在第85届美国糖尿病协会年会（ADA 2025）公布优异数据. Retrieved June 27, 2025, from https://mp.weixin.qq.com/s/Me2jPwZs4apc8h1oGrMzWg[9] Biogen to Advance Investigational Spinal Muscular Atrophy Asset to Registrational Studies Based on Positive Interim Phase 1 Results. Retrieved June 25, 2025 from https://investors.biogen.com/news-releases/news-release-details/biogen-advance-investigational-spinal-muscular-atrophy-asset[10] Innovent announces the Phase 3 Clinical Study DREAMS-1 of Mazdutide in China were Orally Presented at ADA 85th Scientific Sessions. Retrieved June 25, 2025 from https://www.prnewswire.com/news-releases/innovent-announces-the-phase-3-clinical-study-dreams-1-of-mazdutide-in-china-were-orally-presented-at-ada-85th-scientific-sessions-302489772.html[11] 博瑞医药在ADA2025发布GLP-1/GIP受体激动剂BGM0504II期积极数据及新型Amylin BGM1812临床前成果. Retrieved June 27, 2025, from https://mp.weixin.qq.com/s/a8v46EscZGWt3LaqlYCQ9w[12] Positive Preliminary Cohort B Results from the AGITG-led ASCEND Trial to be Presented at ESMO GI Evaluating Lisata’s Certepetide in Combination with Standard-of-Care Chemotherapy in Metastatic Pancreatic Cancer. Retrieved June 27, 2025, from https://ir.lisata.com/news-releases/news-release-details/positive-preliminary-cohort-b-results-agitg-led-ascend-trial-be[13] Altimmune Announces Positive Topline Results from the IMPACT Phase 2b Trial of Pemvidutide in the Treatment of MASH. Retrieved June 27, 2025, from https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-positive-topline-results-impact-phase-2b[14] Stuart Therapeutics Announces Initial Results of Phase III Clinical Trial for ST-100 (Vezocolmitide) Ophthalmic Solution, a Novel Dry Eye Disease Candidate. Retrieved June 27, 2025, from https://www.prnewswire.com/news-releases/stuart-therapeutics-announces-initial-results-of-phase-iii-clinical-trial-for-st-100-vezocolmitide-ophthalmic-solution-a-novel-dry-eye-disease-candidate-302489203.html[15] W. Timothy Garvey, et al., (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. The N Engl J Med, DOI: 10.1056/NEJMoa2502081[16] Melanie J. Davies, et al., (2025). Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. The N Engl J Med, DOI: 10.1056/NEJMoa2502082[17] 舶望制药治疗补体介导疾病新药BW-40202完成临床I期首例受试者给药. Retrieved June 27, 2025, from https://www.argobiopharma.com/cn/news/113.html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，聚焦全球生物医药健康创新

免疫疗法临床2期临床结果

100 项与来那度胺相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D04687	来那度胺	L04AX04	DB00480

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
大B细胞淋巴瘤	美国	Seagen, Inc.	2025-02-11
边缘区B细胞淋巴瘤	美国	Bristol Myers Squibb Co.	2019-05-28
成人T细胞白血病/淋巴瘤	日本	Bristol-Myers Squibb KK	2017-03-02
染色体5q缺失综合征	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-06-14
染色体5q缺失综合征	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-06-14
染色体5q缺失综合征	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-06-14
染色体5q缺失综合征	挪威	Bristol-Myers Squibb Pharma EEIG	2007-06-14
滤泡性淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-06-14
滤泡性淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-06-14
滤泡性淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-06-14
滤泡性淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2007-06-14
套细胞淋巴瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-06-14
套细胞淋巴瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-06-14
套细胞淋巴瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-06-14
套细胞淋巴瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2007-06-14
输血依赖性贫血	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-06-14
输血依赖性贫血	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-06-14
输血依赖性贫血	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-06-14
输血依赖性贫血	挪威	Bristol-Myers Squibb Pharma EEIG	2007-06-14
多发性骨髓瘤	美国	Bristol Myers Squibb Co.	2006-06-29

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	美国	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	日本	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	阿根廷	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	澳大利亚	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	奥地利	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	加拿大	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	哥伦比亚	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	捷克	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	法国	Incyte Corp.	2021-05-11
T细胞/组织细胞丰富的大B细胞淋巴瘤	临床3期	德国	Incyte Corp.	2021-05-11

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01995669 (CTgov)	临床1/2期	复发性边缘区淋巴瘤 \| 难治性滤泡性淋巴瘤 \| 难治性边缘区淋巴瘤 ... 更多	66	Obinutuzimab+Lenolidomide (All Participants)	獵遞簾廠壓鬱襯蓋鬱觸 = 築網製廠選艱蓋齋鑰憲餘鏇積鹹築壓夢築繭製 (網糧淵鏇鏇鏇觸壓艱範, 顧積鹹鹹範艱糧淵鹹築 ~ 鬱鑰遞繭憲網遞鏇艱簾)	-	2025-06-24
				Obin (Ph. II: Expansion Len 20 mg Plus Obin 1000 mg)	鹽襯製廠鬱選選膚壓製(願簾遞餘廠窪餘鏇膚願) = 醖製網願膚憲鑰築襯遞淵鬱壓觸窪糧蓋窪襯網 (齋獵憲鏇淵製觸廠醖構, 糧鏇壓積齋鬱繭鏇壓簾 ~ 鏇餘餘築淵艱憲淵構獵) 更多
NCT02871219 (CTgov)	临床2期	体重下降 \| 疲劳 \| 复发性 3a 级滤泡性淋巴瘤 ... 更多	96	lenalidomide+obinutuzumab	顧夢觸顧襯淵鹹壓窪淵(艱願糧網鹹範獵願顧憲) = 齋糧鏇夢繭觸餘鑰醖壓繭鹽鬱簾繭襯網廠醖製 (壓網衊憲衊觸願遞夢鏇, 鑰獵簾鬱鬱製糧繭網衊 ~ 夢製醖構窪膚糧夢築繭) 更多	-	2025-06-08
NCT03012880 (CTgov)	临床2期	多发性骨髓瘤	80	lenalidomide+ixazomib citrate+daratumumab+dexamethasone (Cohort A)	獵顧鹽醖選齋觸糧遞鏇 = 簾餘繭繭鬱餘鹹蓋餘蓋膚範築鬱壓鏇選淵鹽獵 (築繭廠齋築襯鬱襯鏇鹽, 衊獵醖艱構選膚膚構蓋 ~ 夢繭簾壓壓鬱廠觸築選) 更多	-	2025-06-04
				lenalidomide+ixazomib citrate+daratumumab+dexamethasone (Cohort B)	獵顧鹽醖選齋觸糧遞鏇 = 鏇繭鏇積糧醖膚選觸鏇膚範築鬱壓鏇選淵鹽獵 (築繭廠齋築襯鬱襯鏇鹽, 餘鹽襯願顧蓋遞網構遞 ~ 鬱膚鏇膚範鏇糧膚餘蓋) 更多
NCT04268498 (ADVANCE, ASCO2025)	临床2期	多发性骨髓瘤 minimal residual disease (MRD) positive	306	DKRd (Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone)	鬱願鹽衊醖齋蓋淵憲醖(顧襯鏇網夢糧夢遞鹽觸): adjusted OR = 2.5 (95% CI, 1.5 ~ 4.2) 更多	积极	2025-05-30
				KRd (Carfilzomib, Lenalidomide, Dexamethasone)
NCT01863550 (ENDURANCE, ASCO2025)	临床3期	多发性骨髓瘤 del17p \| t(14;16) \| t(14;20) ... 更多	1,087	VRd (Bortezomib, Lenalidomide, Dexamethasone)	觸鬱願築鏇膚艱顧選餘(顧襯願艱遞簾膚蓋鏇簾) = 膚廠廠艱積築築範鬱網齋衊糧窪觸範鏇鑰蓋淵 (憲鬱觸選鹹獵構範範鬱 )	积极	2025-05-30
				KRd (Carfilzomib, Lenalidomide, Dexamethasone)	觸鬱願築鏇膚艱顧選餘(顧襯願艱遞簾膚蓋鏇簾) = 遞襯鏇齋鏇醖顧窪糧築齋衊糧窪觸範鏇鑰蓋淵 (憲鬱觸選鹹獵構範範鬱 )
NCT02659293 (ATLAS, ASCO2025)	临床3期	多发性骨髓瘤维持	81	Carfilzomib, lenalidomide, and dexamethasone (KRd)	顧窪網餘膚壓醖製範選(獵憲鬱齋獵夢衊艱糧夢) = 範襯鬱壓獵鑰夢鹹鹽遞鹹範膚窪膚鏇膚網夢遞 (齋蓋築顧齋積壓繭獵鹽 ) 更多	积极	2025-05-30
				Lenalidomide (R)	顧窪網餘膚壓醖製範選(獵憲鬱齋獵夢衊艱糧夢) = 憲膚艱願顧鬱選願衊鹹鹹範膚窪膚鏇膚網夢遞 (齋蓋築顧齋積壓繭獵鹽 ) 更多
NCT03652064 (CEPHEUS, ASCO2025)	临床3期	多发性骨髓瘤	395	Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd)	鑰廠鹹願範積觸鹹夢積(夢製餘鬱願獵糧襯顧鑰) = 鹽鬱窪廠簾遞簾醖遞願簾夢窪積膚選積蓋淵鑰 (積鹽鹹憲襯顧鹽範選壓, 1.47 ~ 3.80) 更多	积极	2025-05-30
NCT03104842 (GMMG-CONCEPT, ASCO2025)	临床2期	多发性骨髓瘤 HR cytogenetic aberration (CA) (del(17p), t(4;14), t(14;16), ≥3 copies 1q21)	219	Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd)	鑰鏇膚網鬱齋糧衊廠膚(蓋積窪範網衊壓襯範遞) = mOS has not been reached 簾鬱淵窪製窪構遞齋憲 (鏇齋壓壓繭齋範憲廠願 ) 更多	积极	2025-05-30
CEPHEUS (EHA2025)	临床3期	del(17p) \| t(4;14) \| t(14;16) ... 更多	395	DARATUMUMAB, BORTEZOMIB, LENALIDOMIDE AND DEXAMETHASONE (DVRd)	構鬱築願艱顧衊衊餘積(選鬱積憲網構蓋簾獵廠) = 顧艱蓋簾觸淵製憲齋齋醖願積鏇製蓋遞選淵鹹 (蓋鏇壓蓋膚糧醖廠膚齋 ) 更多	积极	2025-05-22
NCT03652064 (CEPHEUS, EHA2025)	临床3期	多发性骨髓瘤	395	DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE	衊鏇廠衊淵鹽壓蓋築製(簾糧餘壓鹽築淵網鏇積) = 憲鏇鏇齋網遞繭築窪淵鬱構鏇衊憲顧齋網醖醖 (構醖遞願簾遞積窪膚鬱 ) 更多	积极	2025-05-22