A Multicentre, Adaptive, Randomised, Multidomain, Platform Trial for Dose Optimization in the Treatment of Adult Patients With Haematological Diseases (BLOOD-dose): Core Protocol

BLOOD-dose is a multicentre, adaptive, randomized, multidomain platform trial designed to optimize treatment dosing strategies in adult patients with haematological diseases.
The BLOOD-dose core protocol outlines the overall clinical trial design that applies to all included interventions, while domain-specific appendices (DSA) detail the unique characteristics of each domain and specify domain-specific interventions.
New domains will be incorporated over time to address distinct dose-optimization research questions across different haematological conditions and interventions.

开始日期2027-03-01

申办/合作机构

Rigshospitalet

NCT07657312

/ Not yet recruiting临床2期IIT

Phase 2 Study of Cytokine Release Syndrome Prophylaxis With Infliximab for Teclistamab/Talquetamab Therapy in Patients With Relapsed/Refractory Myeloma

This phase II trial tests how well giving infliximab works for the prevention of cytokine release syndrome (CRS) during treatment with teclistamab or talquetamab in patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). CRS and neurologic toxicity (damage to the nervous system which includes the brain, spinal cord, and nerves) are potential risks of treatment with talquetamab and teclistamab. CRS involves a release of a large amount of proteins into the bloodstream causing inflammation. This may cause changes in blood pressure and heartbeat, flu-like symptoms (nausea, fever, and chills), and/or affect the lung/liver/kidney function. It may also cause certain brain-related symptoms, such as dizziness, weakness, confusion, difficulty speaking, and/or decreased brain function (possible paralysis and/or coma). Infliximab is a drug that prevents the tumor necrosis factor-alpha (TNF-α) from working. TNF-α is a cytokine, or chemical messenger, that helps your immune system produce inflammation. Giving infliximab may work well for the prevention of cytokine release syndrome during treatment with teclistamab or talquetamab in patients with relapsed or refractory multiple myeloma.

开始日期2026-08-01

申办/合作机构

Ohio State University Comprehensive Cancer Center

[+2]

NCT07029776

/ Not yet recruiting临床2期

A Phase 2 Study Exploring the Use of Bispecific Antibodies to Improve Progression Free Survival in Patients With High-Risk Newly Diagnosed Multiple Myeloma (MMulti-Immune HR)

The purpose of this research is to learn whether using teclistamab and talquetamab at different time points will improve survival in participants with high-risk Multiple Myeloma (MM).
The treatment on this study will consist of Induction chemotherapy and stem cell collection, Immunotherapy 1 chemotherapy and Immunotherapy 2 chemotherapy. For participants whose testing show they are Minimal Residual Disease (MRD) positive (still have myeloma cells present in the bone marrow testing), a Melphalan-based stem cell transplant will be performed. For participants whose testing show they are MRD negative, the stem cell transplant will not be performed. All participants will go on to receive Immunotherapy 3 chemotherapy, Immunotherapy 4 chemotherapy, and Maintenance therapy.

开始日期2026-07-01

申办/合作机构

Janssen Research & Development LLC

100 项与塔奎妥单抗相关的临床结果

登录后查看更多信息

100 项与塔奎妥单抗相关的转化医学

登录后查看更多信息

100 项与塔奎妥单抗相关的专利（医药）

登录后查看更多信息

129

项与塔奎妥单抗相关的文献（医药）

2026-12-31·JOURNAL OF MEDICAL ECONOMICS

Costs per responder for patients with relapsed or refractory multiple myeloma treated with Talquetamab compared with usual care

Article

作者: Mu, Fan ; Patel, Neel ; Yang, Chelsey ; Jiao, Tianze ; Liu, Yi-Hsuan ; Wang, Jiamin ; Grajales-Cruz, Ariel F. ; Zhang, Xinke ; Lee, Hans C. ; Goble, Joseph

AIMS:

To evaluate costs per responder for patients with triple-class exposed (TCE) relapsed or refractory multiple myeloma (RRMM) receiving talquetamab (Tal) on weekly (QW) and biweekly (Q2W) dosing schedules, compared with usual care from a United States commercial payer's perspective.

METHODS:

A cost per responder model was developed over a 6-month time horizon, incorporating pre-progression and post-progression costs. For Tal QW and Tal Q2W, pre-progression costs included costs of drug acquisition, inpatient step-up doses (hospitalization, pre-medication, and tocilizumab), outpatient visits, and monitoring. Pre-progression costs for usual care were estimated based on a weighted average of the 10 most used regimens in a real-world LocoMMotion/MoMMent study, including costs of acquisition, administration, co-medication, and monitoring. Post-progression costs included subsequent treatment for a subset of patients and terminal care costs prior to death. All costs were reported in 2025 United States Dollars. Clinical data of overall response rate (ORR), progression-free survival, and overall survival were obtained from an indirect treatment comparison using MonumenTAL-1 (September 2024 data cut) and LocoMMotion/MoMMent (October 2022 and August 2023 data cuts) as data sources. Deterministic sensitivity analyses and scenario analyses were conducted to assess the robustness of model results.

RESULTS:

Over the 6-month period, the total cost of care was $179,556 for usual care, $295,993 for Tal QW, and $315,135 for Tal Q2W. Despite higher costs, Tal demonstrated superior ORR, resulting in lower cost per responder: $575,962 for usual care, $405,470 for Tal QW, and $443,165 for Tal Q2W, representing a 23-30% reduction in cost per responder with Tal. Sensitivity and scenario analyses showed consistent findings.

CONCLUSION:

Although Tal QW and Q2W are associated with higher total per-patient costs compared with usual care, they offer improved clinical effectiveness, resulting in lower cost per responder. These findings suggest greater economic value for Tal in the treatment of TCE RRMM.

2026-06-01·EUROPEAN JOURNAL OF HAEMATOLOGY

Salvage Therapy in Multiple Myeloma With Prior T‐Cell Engager Exposure: Talquetamab, Elranatamab or Teclistamab in Combination With Pomalidomide

Article

作者: Phull, Pooja ; Siegel, David ; Biran, Noa ; Parmar, Harsh ; Di Palma‐Grisi, James ; Vesole, David

ABSTRACT:

Multiple myeloma (MM) is a hematologic malignancy manifested by proliferation of clonal plasma cells leading to end‐organ damage. Despite significant advancements in therapeutics, it remains incurable. Cellular therapies such as chimeric antigen receptor (CAR‐T) therapy and T‐cell engager (TCE) therapies have delivered high overall response rates, but almost all patients relapse and subsequent options are limited particularly in view of the increasing prevalence of prior exposure to anti‐BCMA agents and immunomodulator (IMiD) therapies. Our retrospective review of 12 patients between January 2024 and December 2025 who received a combination of talquetamab, elranatamab, or teclistamab with pomalidomide found that 11 of 12 had an overall response, of whom 6 had very good partial response or better at median follow‐up of 9.9 months. All 12 patients were prior exposed to pomalidomide, of whom 10 had been exposed to prior CAR‐T with a median of 7 prior lines of therapy. Safety profiles were favorable: 6 patients experienced Grade 1 CRS, 7 experienced Grade III neutropenia, and 7 of 8 patients receiving talquetamab experienced on‐target, off‐tumor side effects like dysgeusia and skin dryness.

2026-06-01·JCO Oncology Practice

Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses

Article

作者: Giralt, Sergio ; Mailankody, Sham ; Shah, Gunjan L. ; Mitchell, Aaron ; Modelevsky, Lisa ; Landau, Heather J. ; Tan, Carlyn R. ; Patel, Dhwani ; Korde, Neha ; Firestone, Ross S. ; Hashmi, Hamza ; Hultcrantz, Malin L. ; Chan, Amelia ; Hamadeh, Issam S. ; Scordo, Michael ; Rajeeve, Sridevi ; Wang, Alice X. ; Hassoun, Hani ; Shekarkhand, Tala ; Lesokhin, Alexander M. ; Shah, Urvi A. ; Usmani, Saad Z. ; Maclachlan, Kylee

PURPOSE:

Talquetamab is a G protein–coupled receptor class C group 5 member D T-cell–engaging antibody, approved for relapsed/refractory multiple myeloma (RRMM). In the MonumenTAL-1 clinical trial, cytokine release syndrome (CRS) occurred at a frequency of 77%; however, there was no assessment of CRS rates by step-up dose. The primary objective of this study was to characterize CRS rates after each talquetamab step-up dose in a real-world setting.

METHODS:

Patients with RRMM who completed the talquetamab once a week or once every 2 weeks step-up dosing schedule between September 2023 and November 2024 were identified via the institutional database. CRS rate after each talquetamab step-up dose was compared using the chi-square/Fisher’s exact test. The Kruskal-Wallis test was used to compare difference in median time to the CRS onset. Multivariate logistic regression analysis was performed to identify predictors of CRS.

RESULTS:

Fifty patients completed the talquetamab step-up dosing phase during the study period; CRS occurred at a rate of 80%. Pairwise comparisons revealed significant differences in CRS rates between the fourth dose (4%) and each of step-up dose 1 (28%, P = .014) and 2 (34%, P = .003). The only CRS event with fourth dose was grade 1. The median time to onset of first CRS did not differ significantly between step-up doses ( P = .441). Previous exposure to T-cell–redirecting therapy had no impact on CRS incidence (odds ratio: 0.20 [95% CI, 0.03 to 1.10]).

CONCLUSION:

Our findings suggested that the fourth talquetamab dose could be administered in outpatient settings given its high tolerability. The reduced hospitalization period for talquetamab step-up dosing could reduce health care expenses.

626

项与塔奎妥单抗相关的新闻（医药）

2026-06-26

·HELLA环球医讯通

精准靶向疗法之“双特异性抗体（BsAb）”赛道深度起底：一支中国抗体，干翻了全球“药王”？

导读：一边是“摇钱树”——单品一年能卖出几十亿美元；一边是“火药桶”——动辄数十万美元的疗程价格、汹涌的副作用与悬而未决的疗效之争。双抗，这门让全球巨头又爱又怕的生意，正在被一群中国玩家重新洗牌。本文带你把它一次看懂。 01 场景 · 当“药王”第一次被单挑掀翻 2024 年 9 月，全球肿瘤学界被一条消息点燃。一款名叫“依沃西单抗（ivonescimab）”的中国双抗，在一项头对头三期临床试验里，正面击败了被称为全球“药王”的 K 药（帕博利珠单抗 / Keytruda）。 K 药有多大？ 2024 年它卖了约 295 亿美元，是当年全球销量第一的处方药，几乎撑起了默沙东近一半的营收。而在此之前，从没有任何一款药能在头对头三期试验里把它单独掀翻。打破纪录的，是来自中国的康方生物。在这项代号 HARMONi-2 的中国人群试验里，依沃西单抗把患者“疾病不进展”的中位时间从 K 药的 5.8 个月拉长到 11.1 个月，疾病进展或死亡风险下降约 49%。一时间，“药王被中国药掀翻”的叙事传遍全球。图 1：HARMONi-2 三期试验中，双抗依沃西单抗在无进展生存期上显著优于 K 药（中国人群）。但故事远没有这么简单。这场胜利的背后，既有一条正在改写全球免疫治疗格局的技术路线，也藏着一个直到 2025 年才被市场看清的“暗面”。要看懂这一切，得先把“双抗”这门生意拆开来看。药王的护城河第一次被人趟进来——而这个人，来自中国。 02 全景 · 一张万亿赛道的地图先说清楚什么是“双抗”。传统单克隆抗体（单抗）只能识别一个靶点，像一把只能开一把锁的钥匙；双特异性抗体则被工程化改造出“两只手”，可以同时抓住两个不同的目标。最经典的玩法，是一只手抓住癌细胞、另一只手拽住免疫细胞，把“杀手”硬拉到“敌人”面前逼它动手——这是单抗做不到的。术语 · 双抗 / BsAb Bispecific Antibody。能同时结合两个不同抗原或表位的人工抗体，常用于“桥连”免疫细胞与肿瘤细胞，或同时阻断两条致病通路。图 2：以 T 细胞衔接器（TCE）为例，双抗一端结合肿瘤抗原、一端拽住 T 细胞。这门生意有多大？据多家市场机构测算，2024 年全球双抗市场规模约为 115–125 亿美元，其中肿瘤约占三分之二，北美一地就拿走了近九成份额。至于未来——不同机构的预测分歧极大：保守者认为 2034 年约 170 亿美元，激进者则喊出近 4800 亿美元。口径差异如此之大，本身就说明这是一个尚未定型、想象空间巨大的早期赛道。如果按销售额给现存双抗排个座次，你会发现一个反常识的事实：卖得最好的两款双抗，根本不是抗癌药。图 3：销冠 Hemlibra（血友病）与 Vabysmo（眼病）远超抗癌双抗；销售额按各公司年报及公开口径整理。榜首的 Hemlibra（艾美赛珠单抗，血友病）与第二的 Vabysmo（法瑞西单抗，眼底病变）都来自罗氏。这并非巧合，而是一种值得拆解的商业模式：罗氏既不靠“最热闹的抗癌赛道”取胜，也不追逐短期爆款，而是把双抗这种“工程化平台技术”嫁接到自己最深的两块根据地——血液病与眼科，做成可以连续卖十年以上的长周期品种，再用自家诊断业务为这些药精准筛选病人。对中国与新兴药企，这套打法至少有三点可借鉴： · 其一，平台技术要落在自己有临床与商业纵深的疾病领域，而非一窝蜂挤同一个靶点； · 其二，“诊断 + 治疗”协同能显著抬高单品天花板与黏性； · 其三，用“专利接力 + 适应症滚动扩展”延长品种生命周期，而不是把宝全押在一次性的上市冲刺上。从全球格局看，美国是绝对核心、欧洲增速可期、日本是技术源头、印度主打可及性，而中国，正在从“跟随者”变成“爆点制造者”。下面这张表是它们各自的站位。市场角色定位代表企业 / 产品一句话看点美国绝对核心安进 Blincyto、罗氏、强生 Tecvayli 约占全球双抗市场近九成份额，FDA 审批最快、定价最高欧洲增速看好 Genmab（丹麦）、EMA 监管体系全球首款双抗曾在欧获批，多家机构预计未来增速领先日本技术源头中外制药 Chugai（Hemlibra 发明方）抗体工程底蕴深厚，是“药王级”双抗背后的技术策源地之一中国创新爆点康方、三生、普米斯、礼新等 PD-1×VEGF 引爆全球，密集对外授权出海；同时面临医保压价印度可及为先以生物类似药与产能见长本土原研双抗起步，市场随癌症负担上升而打开表 1：全球主要市场在双抗赛道中的角色分布。最赚钱的双抗不在肿瘤科，而在血液科和眼科——这恰恰说明，赛道的金矿还远未被挖完。 03 王牌 · 拆解“摇钱树”与“天价单” 先看真正的现金牛 Hemlibra（艾美赛珠单抗）。它由日本中外制药发明、罗氏推向全球，2017 年获 FDA 批准，靶向凝血因子 IXa 与 X，模拟人体缺失的凝血因子 VIII，用于 A 型血友病。适应症与销售：从“有抑制物”患者扩展到“无抑制物”患者后，用药人群大幅扩容。2024 年它录得约 45 亿瑞士法郎（约 50 亿美元）销售额，稳居全球双抗销冠，也是单品年销的“天花板”级存在。专利与争议：作为皮下注射、给药频率低的长效产品，它替代了传统需要频繁静脉输注的凝血因子，极大改善患者生活质量；但也正因疗效突出、价格高昂，关于其长期成本、与传统疗法的性价比之争一直存在——这也是所有“改变标准”的高价生物药都要面对的共同课题。再看一张“天价单”——强生的 Tecvayli（teclistamab），2022 年获批，是首款靶向 BCMA×CD3 的双抗，用于多发性骨髓瘤。它的公开标价约为每月 39,500 美元，按临床中位用药时长测算，单个疗程总花费常常落在 35.5 万至 39.5 万美元区间（折扣前）。术语 · PFS 与 OS PFS（无进展生存期）指疾病不恶化的时间；OS（总生存期）指患者实际活了多久。监管与医生通常更看重 OS——它才是“真正活得更久”的金标准。一句话总结这一段：双抗里既有像 Hemlibra 那样把一个适应症做深做长的“慢牛”，也有像 Tecvayli 那样定价惊人、却把救命门槛标到数十万美元的“天价单”。前者是商业模式的胜利，后者则把支付与可及性的矛盾摆上了台面。一支药每月报价近四万美元——它救的是命，掏空的也可能是一个家庭。 04 护城河 · 平台、管线、并购与专利双抗是典型的“平台型”生意，真正的护城河不在某一款药，而在四件事：技术平台、研发管线、并购布局、专利策略。技术平台：安进的 BiTE（T 细胞衔接器）、罗氏的 CrossMab、Genmab 的 DuoBody、康方的四聚体双抗平台等，各家用不同的“分子骨架”解决同一道工程难题——如何让两只手稳定、低毒地同时工作。平台一旦跑通，就能像流水线一样批量产出新分子。研发管线：从血液瘤（白血病、淋巴瘤、骨髓瘤）向实体瘤、再向自身免疫病外溢，是当前最清晰的扩张方向；同时，“双抗 × ADC（抗体偶联药物）”的融合疗法也在快速立项。并购与授权：这是过去一年最劲爆的看点。自从中国康方的 PD-1×VEGF 双抗掀翻 K 药，跨国巨头开始排队“扫货”中国资产——它们不是在买一款药，而是在买“别错过下一个药王”的入场券。图 4：近一年代表性 PD-(L)1×VEGF 双抗对外授权 / 收购（交易潜在总额，按公开披露整理）。专利策略：双抗的专利壁垒既包括分子序列与结构，也包括平台技术、生产工艺与组合用法。谁能把“靶点组合 + 工程骨架 + 适应症”织成一张密网，谁就能把后来者挡在门外更久——这也是平台公司估值远高于单品公司的根本原因。买双抗不是买一款药，而是买一张“别错过下一个药王”的门票。 05 暗面 · 神话裂缝、副作用与天价之争现在回到开头那场胜利的“暗面”。 2025 年，依沃西单抗的全球三期试验 HARMONi 读出了关键数据：它在 PFS（无进展生存期）上依旧亮眼，但在 OS（总生存期）这一金标准上未能达到统计学显著。换句话说，“疾病晚点恶化”被证明了，“患者真的活得更久”却还没被证明。消息一出，其美国合作方 Summit 的股价在不同时点出现过约 26%—37% 的暴跌。更尖锐的争议在于：HARMONi-2 的惊艳数据来自中国人群，而中国与西方患者在肺癌驱动基因（如 EGFR 突变）上的分布差异明显。中国的胜利能否原样复制到西方人群，至今仍是悬在这条赛道头上的最大问号。副作用是第二道暗面。以 T 细胞衔接类双抗为例，强行激活免疫系统会引发“细胞因子释放综合征（CRS）”和神经毒性。以 Tecvayli 的关键试验为例，CRS 发生率约 72%、神经系统毒性约 57%，因此其说明书带有显著的安全性警示。强效与高风险，往往是同一枚硬币的两面。术语 · CRS · 细胞因子释放综合征免疫细胞被大量激活后“火力全开”，释放过量细胞因子，可引起高热、低血压乃至危及生命，是 T 细胞衔接类疗法最受关注的副作用。第三道暗面来自历史。全球第一款双抗 Catumaxomab 早在 2009 年就在欧洲获批，却于 2017 年因商业原因黯然退市。它提醒所有人：技术上的“第一”，并不等于商业上的“活下来”。第四道是中国市场的博弈。高价创新药与医保控费之间的张力长期存在；与此同时，K 药自身的专利悬崖临近、皮下剂型与生物类似药蓄势待发——这意味着，等到这些双抗真正放量时，它们要抢的可能已不再是那块最肥的蛋糕。证明“病情晚点恶化”很容易，证明“病人真能多活几年”才是真正的生死线。 06 中国故事 · 与未来十年的机会和危机把镜头拉回中国。过去一年里，中国双抗完成了一次身份切换：从“仿制与跟随”，变成“原创与出海”。康方、三生、普米斯、礼新等公司的核心资产，被 BioNTech、默沙东、辉瑞等巨头以重金收入囊中——这是中国创新药第一次在一个全球最热的肿瘤靶点上掌握定价权。竞合关系也变得微妙：跨国巨头一边在中国市场与本土药企正面竞争，一边又反过来买入中国资产为自己的全球管线“补课”。中国药企则借出海拿到现金流与全球临床的入场券。这是一场谁也离不开谁的“竞合”。展望下一个十年，机会有三： · 一是 PD-1×VEGF 等新型双抗若能在西方人群证明 OS，将真正动摇 K 药的统治； · 二是双抗向自身免疫等大病种外溢，打开远超肿瘤的市场； · 三是“双抗 × ADC”等融合疗法，可能孕育下一代爆款。危机同样有三： · 一是靶点扎堆、同质化内卷，几十款 PD-1×VEGF 同台竞技，多数注定陪跑； · 二是支付难题——数十万美元的疗程如何与医保和商保共处； · 三是安全性与长期获益的不确定性，任何一次大型试验的“暗面”都可能让市值一夜蒸发。双抗的故事，本质上是一场关于“工程化生命科学”的豪赌：用更聪明的分子设计，去换更确定的疗效与更长的专利寿命。中国，已经第一次坐到了牌桌的主位上。中国创新药第一次不是在追赶药王，而是在定义“谁有资格成为下一个药王”。留言聊聊如果你来下注，你更看好哪一种结局？ ① 中国双抗会跑出真正的全球“药王”，改写肺癌一线治疗； ② 它们终将倒在“总生存期”这道坎上，沦为又一轮资本故事； ③ 真正的赢家不是某一款药，而是默默卖“铲子”的平台与生产方。欢迎在评论区写下你的判断与理由。 ↓ The End 数据来源与时间 1. 罗氏（Roche）2024 年度业绩公告，2025-01-30：Hemlibra 2024 年销售约 45 亿瑞郎；Vabysmo 约 39 亿瑞郎。 2. 默沙东（Merck）2024 第四季度及全年财报，2025-02-04：Keytruda 2024 年全球销售约 295 亿美元。 3. Summit Therapeutics 公告及多家医药媒体（STAT、Fierce Pharma），2024-09-08：HARMONi-2 中位 PFS 11.1 vs 5.8 个月、进展风险下降约 49%。4. Summit Therapeutics 8-K 及 Fierce Pharma / BioSpace，2025-05-30 至 2025-09：全球 HARMONi 试验 OS 未达统计学显著，合作方股价大幅波动。5. Fierce Pharma、Pharmaphorum、BioSpace，2025-05-20：辉瑞–三生制药 SSGJ-707 授权，首付款 12.5 亿美元、潜在总额约 60 亿美元；默沙东–礼新（LM-299）首付款 5.88 亿美元；BioNTech–普米斯（BNT327）潜在总额约 9.5 亿美元。6. Fierce Pharma，2024-01：强生 Tecvayli 标价约每月 39,500 美元。7. FDA / PubMed 审批摘要，2024：teclistamab 关键试验 CRS 约 72%、神经毒性约 57%。8. Amgen 及 GlobeNewswire，2024-02-29：Blincyto 2023 年销售约 8.61 亿美元；Catumaxomab 于 2017 年因商业原因退市。9. Genmab 2024 年报，2025-02-12：Epkinly/Tepkinly 2024 年全球销售约 2.81 亿美元。10. Precedence Research、Roots Analysis、Towards Healthcare 等市场报告，2025：全球双抗市场规模、增速、北美占比约 88%、肿瘤占比约 2/3 及已获批双抗数量。说明：因汇率与统计口径不同，文中销售额均为约数；瑞郎/美元按近似汇率换算。市场规模为多家机构区间估计，仅供参考。免责声明本文为医药行业科普与商业分析，不构成任何投资建议或诊疗建议。所涉药物均须在医生指导下使用；涉及具体病情请咨询专业医疗机构。文中市场数据来自公开资料，可能存在口径与时间差异，请以企业官方披露为准。文中部分配图来源网络，仅作展示，如有侵权，请联系删除。原创声明本文为原创内容，所有文字均为本号独立撰写、制作。转载授权：欢迎转发分享至朋友圈；未经授权，禁止以任何形式转载、摘编或二次加工。转载与商务合作请在后台联系我们。记得点分享、收藏、在看、点赞哦！

2026-06-26

·BioSpace

CHMP recommendation advances Johnson & Johnson’s TECVAYLI®▼ (teclistamab) plus daratumumab as a potential standard of care for relapsed/refractory multiple myeloma

Recommendation supported by unprecedented Phase 3 data, demonstrating that TECVAYLI ® in combination with daratumumab achieved statistically significant improvements in progression-free and overall survival versus standard of care 1 Pending approval, this novel complementary immunotherapy combination is positioned to delay disease progression for patients treated as early as second line, with 83% of patients alive at three years 1 BEERSE, BELGIUM, June 26, 2026 (GLOBE NEWSWIRE) -- Johnson & Johnson today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of an indication extension of TECVAYLI ® (teclistamab) in combination with daratumumab for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy. Advancing complementary immunotherapies to improve patient outcomes Teclistamab and daratumumab work in a mechanistically complementary manner by engaging multiple tumour and immune directed pathways. 1,2 When combined, daratumumab modulates the immune system to create a more favourable immune microenvironment and enhances T-cell fitness and activation, amplifying teclistamab-mediated killing of myeloma cells. 1,2 This combination improves patient outcomes by using immunotherapies earlier in the treatment journey when patients’ immune systems are more robust. 1, 2 Expert and company perspectives support the earlier use of teclistamab combination in multiple myeloma care “Unprecedented data show a meaningful extension in overall survival and minimal progression events observed after the first six months. More than 90% of patients receiving the combination who were progression-free at six months remained progression-free at three years, highlighting the potential for durable long-term disease control.” said Ester in ’t Groen, EMEA Therapeutic Area Head, Haematology, Johnson & Johnson. “This CHMP opinion marks an important step towards establishing the off-the-shelf immunotherapy combination of teclistamab plus daratumumab as a new standard of care earlier in the treatment pathway for multiple myeloma.” “At Johnson & Johnson our ambition is to leverage the full potential of our comprehensive multiple myeloma portfolio, to strengthen patient outcomes at every stage of the treatment continuum,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "By advancing innovative immunotherapies such as teclistamab and combining them with a well-established standard of care like daratumumab, we are building on our deep scientific expertise to deliver more integrated, combination-based approaches that can continue to raise expectations for patient care.” Teclistamab plus daratumumab SC achieves meaningful and sustained improvements in patient outcomes The CHMP recommendation is supported by data from the Phase 3 MajesTEC-3 study ( NCT05083169 ), evaluating the efficacy and safety of teclistamab plus daratumumab subcutaneous (SC) formulation versus investigator’s choice of daratumumab SC and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients who have received 1–3 prior lines of therapy. 3 At nearly three years of follow-up, results show an 83.4% reduction in the risk of disease progression or death in patients treated with teclistamab plus daratumumab SC, compared to standard of care (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12-0.23; p <0.0001). 1 More than 90% of patients who remained progression-free at six months (n=249) remained progression-free at three years, demonstrating sustained disease control over time. 1 Overall survival (OS) favoured teclistamab plus daratumumab SC (HR, 0.46; 95% CI, 0.32-0.65; p <0.0001), with treatment benefit observed across all prespecified subgroups. 1 ,2 At three years, OS rates were 83.3% for the combination and 65.0% for standard of care. 1 Both progression-free survival and OS benefits were clinically meaningful and statistically significant. 1 Manageable safety pro with teclistamab combination Teclistamab plus daratumumab SC demonstrated a safety pro with the well-known profiles of the individual therapies. 1 , 3 , 4 All cases of cytokine release syndrome were Grade 1/2, did not lead to treatment discontinuation, and were manageable and resolved. 1 Rates of Grade 3/4 treatment-emergent adverse events (TEAEs) were comparable to standard of care regimens (95.1% vs. 96.6%) with cytopenia and infection most commonly observed. 1 Grade ≥3 infections decreased over time with the use of immunoglobulin supplementation and infection prophylaxis, along with a switch to monthly dosing. 2 Discontinuations due to TEAEs were low and similar between study arms (4.6% vs. 5.5%). 1 About the MajesTEC-3 Study MajesTEC-3 ( NCT05083169 ) is an ongoing, Phase 3 randomised study evaluating the safety and efficacy of teclistamab plus daratumumab subcutaneous (SC) (n=291) versus investigator’s choice of daratumumab SC and dexamethasone with either pomalidomide or bortezomib (n=296) (DPd/DVd) in patients with relapsed or refractory multiple myeloma (RRMM) who have received 1–3 prior lines of therapy. 5 The primary endpoint is progression-free survival (PFS) and secondary endpoints include complete response or better (≥CR), overall response rate (ORR), minimal residual disease (MRD) negativity (10⁻⁵ by next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. 5 The MajesTEC-3 study is a part of the MajesTEC clinical programme, which includes exploring the potential of teclistamab as a combination regimen. 5 About Teclistamab Teclistamab received European Commission (EC) approval in August 2022 for the treatment of patients with RRMM who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. 6 In August 2023, the EC approved a Type II variation application for teclistamab, providing the option for a reduced dosing frequency of 1.5mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. 7 Teclistamab is an off-the-shelf (or ready-to-use) bispecific antibody. 3 , 8 Teclistamab, a subcutaneous injection, redirects T-cells through two cellular targets (BCMA and CD3) to activate the body’s immune system to fight cancer. 1,3 Teclistamab is currently being evaluated in several combination studies. 5 , 9,10 ,11 To date, more than 26,000 patients have been treated worldwide with teclistamab. 1 2 For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using teclistamab, please refer to the Summary of Product Characteristics at: . ▼ In line with EMA regulations for new medicines and those given conditional approval, teclistamab is subject to additional monitoring. 3 About Daratumumab and Daratumumab SC Johnson & Johnson is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease. In August 2012 , Janssen Biotech, Inc., a Johnson & Johnson company, and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 748,000 patients worldwide. 1 3 Daratumumab was the first CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. 5, 1 4 Daratumumab SC was also the first oncology injectable approved for administration by patients living with multiple myeloma or their caregivers from the fifth dose, if determined to be appropriate by their healthcare professional and following proper training. 5, 15 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE ® drug delivery technology. 5 CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. 5 ,16 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death. 5 Daratumumab may also have an effect on normal cells. 5 Data across ten Phase 3 clinical trials, in both the frontline and relapsed settings across all newly diagnosed multiple myeloma patients, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival. 17,18,19,20,21,22,23,24,25,26 For further information on daratumumab, please see the Summary of Product Characteristics at: . About Multiple Myeloma Multiple myeloma is a complex blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. 2 7 ,2 8 In multiple myeloma, these malignant plasma cells continue to proliferate, accumulating in the body and crowding out normal blood cells, as well as often causing bone destruction and other serious complications. 2 9 , 30 In the European Union, it is estimated that more than 35,000 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died. 31 Patients living with multiple myeloma experience relapses which become more frequent with each line of therapy, while remissions become progressively shorter. 32 , 33 ,3 4 Whilst some patients with multiple myeloma initially have no symptoms, others can have common signs and symptoms of the disease, which can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney damage. 3 5 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at . Follow us at . Cautions Concerning Forward-Looking Statements This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of teclistamab and daratumumab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Key Search Terms MajesTEC-3 Phase 3 clinical trial TECVAYLI Teclistamab DARZALEX Daratumumab Teclistamab and daratumumab combination TECVAYLI and DARZALEX combination Relapsed and or refractory multiple myeloma (RRMM) Early relapse multiple myeloma Second line multiple myeloma treatment First relapse therapy for multiple myeloma Treatment resistance in multiple myeloma Progression-free survival (PFS) in multiple myeloma Overall survival (OS) in multiple myeloma Multiple myeloma Bispecific antibody therapy CD38-targeted therapy BCMA-targeted bispecific therapy Combination immunotherapy EMEA haematology pipeline Multiple myeloma innovation Multiple myeloma treatment END References: 1 Costa L, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2026;394(8):739-752. 2 Mateos MV, et al. Phase 3 Randomized Study of Teclistamab plus Daratumumab Versus Investigator’s Choice of Daratumumab and Dexamethasone with either Pomalidomide or Bortezomib (DPd/DVd) in patients (pts) with Relapsed Refractory Multiple Myeloma (RRMM): Results of the MajesTEC-3 Study. Oral Presentation #06. American Society of Hematology (ASH) Annual Meeting; 06-09 December, 2025. 3 European Medicines Agency. TECVAYLI Summary of Product Characteristics. Available at: . Last accessed: June 2026. 4 European Medicines Agency. DARZALEX Summary of Product Characteristics. Available at: . Last accessed: June 2026. 5 ClinicalTrials.gov. A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-3). Available at: . Last accessed: June 2026. 6 Johnson & Johnson.com. Janssen Marks First Approval Worldwide for TECVAYLI®▼(teclistamab) with EC Authorisation of First-in-Class Bispecific Antibody for the Treatment of Patients with Multiple Myeloma. Available at: . Last accessed: June 2026. 7 Johnson & Johnson.com. European Commission Approves Reduced Dosing Frequency for Janssen’s Bispecific Antibody TECVAYLI®▼ (teclistamab). Available at: . Last accessed: June 2026. 8 Moreau P, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;287(6):494-505. 9 ClinicalTrials.gov. A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma (MajesTEC-2). Available at: . Last accessed: June 2026. 10 ClinicalTrials.gov. A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma. Available at: . Last accessed: June 2026. 11 ClinicalTrials.gov. A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma. Available at: . Last accessed: June 2026. 12 J&J Data on File. Number of Patients Treated with TECVAYLI Worldwide as of March 2026. 13 J&J Data on File. Number of Patients Treated with DARZALEX ® Worldwide as of December 2025. 14 Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX ® (Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: . Last accessed: June 2026. 15 J&J Data on File. DARZALEX® is the first oncology injectable approved for self-administration by patients or caregivers as of March 2026. 16 Fedele G, et al. CD38 ligation in peripheral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and impaired secretion of IFNy cytokines and proliferation. Mediators Inflamm. 2013;564687. 17 Moreau P, et al. Bortezomib, Thalidomide, and Dexamethasone With or Without Daratumumab Before and After Autologous Stem-Cell Transplantation for Newly Diagnosed Multiple Myeloma (CASSIOPEIA): A Randomised, Open-label, Phase 3 Study. Lancet. 2019;394(10192):29-38. 18 Facon T, et al. MAIA Trial Investigators. Daratumumab Plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115. 19 Mateos MV, et al. Overall Survival with Daratumumab, Bortezomib, Melphalan, and Prednisone in Newly Diagnosed Multiple Myeloma (ALCYONE): A Randomised, Open-label, Phase 3 Trial. The Lancet. 2020;395(10218):132-141. 20 Dimopoulos MA, et al. APOLLO Trial Investigators. Daratumumab Plus Pomalidomide and Dexamethasone Versus Pomalidomide and Dexamethasone Alone in Previously Treated Multiple Myeloma (APOLLO): An Open-label, Randomised, Phase 3 Trial. Lancet Oncol. 2021;22(6):801-812. 21 Palladini G, et al. Daratumumab Plus CyBorD for Patients with Newly Diagnosed AL Amyloidosis: Safety Run-in Results of ANDROMEDA. Blood. 2020;2;136(1):71-80. 22 Chari A, et al. Daratumumab Plus Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma. Blood. 2017;130(8):974-981. 23 Bahlis NJ, et al. Daratumumab Plus Lenalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Extended Follow-up of POLLUX, A Randomized, Open-label, Phase 3 study. Leukemia. 2020;34(7):1875-1884. 24 Mateos MV, et al. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Previously Treated Multiple Myeloma: Three-Year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2020;20(8):509-518. 25 Usmani S Z, et al. Daratumumab + Bortezomib/Lenalidomide/Dexamethasone in Patients with Transplant-Ineligible or Transplant-Deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. Oral Presentation. 21 st International Myeloma Society (IMS) Annual Meeting. September 25 – 28, 2024. 26 Sonneveld P, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024; 390(4):301-313. 27 Abdi J, et al. Drug Resistance in Multiple Myeloma: Latest Findings on Molecular Mechanisms. Oncotarget. 2013;4(12):2186-2207. 28 Myeloma UK. What is myeloma? Available at: . Last accessed: June 2026. 29 Lungu O, et al. Mechanistic insights into bone destruction in multiple myeloma: cellular and molecular perspectives. Journal of Bone Oncology. 2025;51:100668. 30 Mayo Clinic. Multiple Myeloma. Available at: . Last accessed: June 2026. 31 ECIS - European Cancer Information System. Estimates of Cancer Incidence and Mortality in 2022, by Country. Multiple Myeloma. Available at: . Last accessed: June 2026. 32 Bhatt P, et al. Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Curr Oncol. 2023;30(2):2322-2347. 33 Hernández-Rivas JÁ, et al. The Changing Landscape of Relapsed and/or Refractory Multiple Myeloma (MM): Fundamentals and Controversies. Biomark Res. 2022;10(1):1-23. 34 McCurdy A, et al. Redefining attrition in multiple myeloma (MM): a Canadian myeloma research group (CMRG) analysis. Blood Cancer Journal. 2023;13(1):111. 35 American Cancer Society. Multiple Myeloma: Early Detection, Diagnosis and Staging. Available at: . Last accessed: June 2026. CP-583164 June 2026 CONTACT: Media contact: Jenni Mildon jmildon@its.jnj.com +44 7920 418 552 Investor contact: Jess Margevich investor-relations@its.jnj.com

临床结果临床3期上市批准引进/卖出免疫疗法

2026-06-25

·新药转化研究

模型引导的药物研发（MIDD）范例——PBPK模型评估DXd的DDI风险：从T-Dxd到Dxd全系列ADC

如何评估ADC类产品的药物-药物相互作用（Drug-Drug Interaction, DDI）是ADC类药物开发过程中必须要回答的问题。传统单抗类药物几乎不参与酶代谢，DDI风险可以忽略；ADC则不同——抗体负责靶向递送，小分子载荷在细胞内外释放，可以成为药物代谢酶和转运体的底物。对于同一载荷被反复使用的ADC产品（如第一三共的DXd类产品），如何用有限的临床DDI研究覆盖这一类产品的合规用药要求，是研发团队面前的现实问题。 DXd为拓扑异构酶I抑制剂，是T-DXd（曲妥珠单抗德鲁替康，trastuzumab deruxtecan）的载荷。体外研究已确认DXd是CYP3A、OATP1B1/1B3、P-gp和BCRP的底物。T-DXd临床DDI研究（DS8201-A-A104）纳入利托那韦（CYP3A/OATP1B双重强抑制剂）和伊曲康唑（CYP3A强抑制剂），两者均只使DXd暴露量上升约1.2倍。Watanabe等（2026）在CPT: Pharmacometrics & Systems Pharmacology发表了对应的PBPK建模研究，将这一临床结果嵌入定量框架，目标是为后续DXd-ADC家族建立可复用的DDI预测平台。本文以该论文为核心，拆解T-DXd的PBPK模型的方法论路径——ADC最小PBPK框架如何搭建、载荷DXd的消除途径如何自下而上量化，以及这套模型如何被FDA审评引用到后续品种Dato-DXd的临床药理学评估中。一、研究背景：ADC的DDI评估困境与PBPK的角色 1.1 ADC的DDI特殊性从MMAE到DXd，监管已经针对ADC载荷的DDI评估积累了一定的经验。MMAE——brentuximab vedotin、polatuzumab vedotin、enfortumab vedotin的共同载荷vedotin是CYP3A底物兼弱效CYP3A抑制剂。Genentech和Seagen的策略是先在brentuximab vedotin上做完整的临床DDI试验，再用PBPK模型为后续MMAE-ADC推导DDI标签，节省了重复临床试验的资源。FDA在对MMAE家族的审评中接受了这一策略，为DXd家族的类似做法提供了参照。 DXd的消除路径更为复杂：体外数据提示同时涉及CYP3A代谢、OATP1B1/1B3摄取转运、P-gp和BCRP胆汁外排，以及肾清除。多条消除通道叠加时，任何单一通道的抑制或诱导理论上可能被其他通道部分代偿。 1.2 临床DDI研究的定量结果 2021年发表的DS8201-A-A104研究在T-DXd 5.4 mg/kg IV给药基础上，分别加入利托那韦（200 mg BID）和伊曲康唑（200 mg BID第1天，继以200 mg QD），评估Cycle 3（抑制剂存在）对比Cycle 2（无抑制剂）的DXd暴露变化。 • 利托那韦组：DXd AUC GMR = 1.22（90% CI: 1.08–1.37），Cmax GMR = 0.987（90% CI: 0.854–1.14） • 伊曲康唑组：DXd AUC GMR = 1.18（90% CI: 1.11–1.25），Cmax GMR = 1.04（90% CI: 0.917–1.18） 1.2倍的AUC增加对于强效抑制剂来说异常偏低——如果DXd主要经CYP3A代谢，加入利托那韦通常AUC会上升3–5倍以上。这个结果本身就是一个信号：DXd消除路径中，CYP3A代谢的贡献远低于预期。 1.3 本研究聚焦的核心问题（1）如何构建一个既描述完整ADC（T-DXd）PK、又刻画释放载荷（DXd）PK的集成PBPK模型？（2）DXd的消除途径中各通道的真实贡献比例是多少？（3）PBPK模型能否精确复现临床1.2倍DDI结果，并说明机制？（4）在缺乏直接DXd静脉给药临床数据的情况下，模型的参数可识别性和预测可靠性如何评估？（5）该模型如何迁移至后续DXd-ADC品种的DDI预测？二、研究设计：临床数据与仿真框架 2.1 临床数据来源建模使用了两项第一三共的T-DXd临床研究数据： DS8201-A-J101（I期剂量递增/扩展）：T-DXd 5.4和6.4 mg/kg Q3W剂量扩展队列PK数据，用于T-DXd和DXd基础PK模型建立。 DS8201-A-A104（DDI专项研究）：5.4 mg/kg Q3W联合利托纳韦和伊曲康唑，评估Cycle 2（基线）vs Cycle 3（抑制剂）的DDI效应，用于酶抑制剂模型构建。 2.2 建模平台全部模拟使用Simcyp Population-Based Simulator V21（Certara），DDI仿真所用的利托那韦和伊曲康唑模型均为Simcyp V21内置默认模型，其中利托那韦模型需额外补充OATP1B1/1B3的Ki值。仿真采用Sim-Japanese人群和Sim-Cancer人群。三、PBPK模型构建：双层架构与参数策略 3.1 T-DXd的最小ADC PBPK模型 ADC的PBPK建模面临一个特有的结构挑战：整个分子由两个药动学行为差异巨大的组分构成——大分子抗体（MW ≈ 150,000 Da）和小分子载荷（DXd，MW = 493.48 Da）。Simcyp的最小ADC PBPK模型提供了一个双层嵌套框架： ADC部分：基于最小PBPK模型描述完整T-DXd的PK，核心机制包括血管外渗透、FcRn介导的内体循环、内体摄取后ADC分解代谢触发DXd释放。载荷部分：释放的游离DXd进入PBPK模型；该模型内嵌肝脏渗透限制（PerL）模型，处理OATP介导的主动摄取和P-gp/BCRP介导的胆汁外排。关键参数来源： • FcRn结合常数（KD1 = 1.39 mM，2:1化学计量）：基于曲妥珠单抗实测数据（1.64 μM）校准。 • Kup = 0.0976 h⁻¹，FR = 0.598：通过拟合5.4 mg/kg的T-DXd临床PK数据进行参数估计获得。 • Frel = 0.5：拟合DXd临床PK数据，机制解释为T-DXd在肝脏降解后释放的DXd直接经P-gp/BCRP泵入胆汁，与食蟹猴数据吻合。 3.2 DXd自下而上的PBPK模型 DXd的PBPK模型采用自下而上的策略构建，依据体外和动物试验中获得的ADME数据建立机制模型，不依赖人体直接给药获得的DXd临床数据。利托那韦的酶抑制PBPK模型：Simcyp默认利托那韦模型不含OATP1B1/1B3的Ki值。研究者从普伐他汀+利托那韦联合给药的临床DDI数据（AUC GMR ≈ 1.7倍）反推利托那韦抑制OATP1B1/1B3 Ki值：Ki(OATP1B1) = 0.043 μM，Ki(OATP1B3) = 0.051 μM。 3.3 模型验证标准 PK预测接受标准：预测/观测比（S/O）在0.5–2倍范围内视为可接受（符合国际PBPK建模报告共识，Shebley et al., 2018）。DDI预测的GMR预测值与观测值之差在0.9-1.1倍以内视为良好。四、研究结果：模型准确性与通路贡献 4.1 基础PK拟合 T-DXd和DXd的基础PK拟合在5.4 mg/kg时，T-DXd AUCtau S/O比为0.79–0.89，Cmax S/O为0.85–0.89，均在2倍范围内。DXd在Frel = 50%条件下AUCtau S/O比为1.13–1.24；6.4 mg/kg剂量的预测性同样良好。Frel = 100%时DXd AUCtau被过高估计（S/O ≈ 1.61–1.77），校正至Frel = 50%后改善显著。 4.2 DDI仿真结果 AUC的GMR预测与观测之差在1.1倍以内，而Cmax的GMR被轻度高估（最高 S/O ≈ 1.34）。产生这一情况的原因是：临床DDI研究中Cycle 3对比的是Cycle 2而非Cycle 1，因此观察到的Cmax的GMR会高于模型模拟的结果。此外，从肿瘤动态变化的机制上来看，随着T-DXd多次给药后肿瘤HER2表达下降、DXd释放减少，导致抑制剂对DXd的Cmax的影响在临床数据中看起来偏小。但目前的PBPK模型未纳入这一动态因素。但这一微小的差异不影响DDI风险等级判断。 4.3 DXd消除路径物质平衡单次直接给予DXd（0.1 mg IV）的模型模拟试验中，各消除途径贡献比例为： • 胆汁外排（P-gp + BCRP）：62.3% • 肾清除：32.6% • CYP3A4代谢：4.8%；其他代谢路径：0.3% 这与非临床数据高度吻合：胆汁插管大鼠14C-DXd胆汁回收率约71.5%，肾排泄约19.8%；食蟹猴粪便（67.3%）/尿液（18.7%）的比例与之接近。CYP3A4只贡献DXd约5%的清除，这直接解释了为何利托那韦和伊曲康唑对DXd暴露的影响如此有限。 4.4 敏感性分析：模型稳健性评估以10倍放大/缩小各药物清除相关参数，评估其对DDI GMR的影响： • CYP3A4代谢速率±10倍：对DDI GMR影响可忽略（验证了CYP3A4贡献占比极低的结论） • OATP1B摄取清除增至10倍：利托那韦DDI预测仍为"弱相互作用"（GMR < 2.0），未超过临床意义阈值 • 外排清除±10倍：伊曲康唑组在外排降低10倍时预测升至"弱相互作用"区间，始终未超过2倍 • 肾清除±10倍：与摄取清除方向相反，幅度有限结论：在现实生理参数范围内，DXd的DDI风险等级（"无临床意义"或最多"弱相互作用"）不依赖于任何单一参数假设。五、批判性分析与可迁移经验 5.1 几个值得深究的问题问题1：Frel参数的可识别性——模型是否在拟合一个自由参数？ Frel = 0.5完全靠拟合DXd临床PK数据得到，没有独立的实验验证。但Frel的取值（0.5 vs 1.0）对DDI GMR预测值几乎没有影响。从本质上讲，DDI评估的是Cycle 3/Cycle 2的比值，只要Frel在有无抑制剂两种情形下保持一致，Frel的值的大小不会影响比值预测。这是一个参数不确定性不影响决策可靠性的典型案例，在其他基于PBPK的DDI 分析中有借鉴价值。问题2：肿瘤负荷的动态变化如何影响模型的时间依赖性预测？模型未纳入TMDD的操作在剂量高于3.2 mg/kg（TMDD饱和）的条件下是合理简化。但DDI研究设计用了Cycle 3对比Cycle 2，此时肿瘤负荷降低且HER2靶点已经下调，ADC内化减少导致DXd释放减少。但这个动态效应被模型忽略，且是Cmax GMR轻度高估的根本原因。因此，对后续应用于低剂量组或HER2低表达患者的预测时，需要重新审视这一假设是否产生影响。问题3：PBPK模型跨ADC使用需要调整哪些参数？ DXd小分子模型可以直接沿用（只要载荷和连接子相同）该模型。ADC层面需要重新参数化的是KD值、DAR值分布、Kup和FR（基于新ADC的PK数据拟合），以及Frel（可能随组织靶向分布不同而变化）。FDA在对Dato-DXd的审评中明确接受了这一借用框架，提供了监管层面的先例认可。问题4：MMAE家族与DXd家族的PBPK策略有何异同？ MMAE是CYP3A底物兼弱效CYP3A抑制剂，DDI风险以双向（perpetrator + victim）评估为主；DXd的DDI风险几乎完全在victim维度，且因多路径清除而天然稀释了CYP3A对其暴露水平的影响。MMAE系列先做brentuximab vedotin的临床DDI验证再外推；DXd系列从一开始就把后续品种的可扩展性纳入建模设计。两套策略路径不同，原理相同，最终均获监管认可。 5.2 对行业的参考价值 ADC载荷的消除路径多样性就会有天然的DDI缓冲效应：当一个小分子有5条以上独立的消除路径且没有任何单一路径占主导，抑制其中任何一条路径的影响都非常有限。DXd就是一个很好的例证。ADC开发中，主动设计"多路径消除"的载荷是降低产品DDI风险的可行方向。 Frel是ADC PBPK建模中的关键不确定性参数，但不妨碍DDI评估可靠性：在没有"载荷单独给药"临床数据的情况下，Frel只能依靠拟合ADC给药后的载荷PK数据估算。敏感性分析结果表明这个参数对DDI比值的预测不敏感，提示了这一不确定性的实际影响有限。监管认可的关键是预测稳健性，而非模型的完美拟合：虽然基于T-Dxd建立的PBPK模型存在已知局限，但FDA仍在Dato-DXd审评中接受了其基于T-Dxd建立的PBPK模型评估DDI的适用性。从这里可以看出，监管审评更关注的是模型对临床核心问题的回答是否可靠，而非每个PK参数的精确拟合。六、启发与展望 T-DXd的PBPK DDI研究是ADC临床药理学/定量药理学严谨方法论的一个缩影。DXd家族的管线规模（T-DXd → Dato-DXd → 多个在研品种）为PBPK“一次建模、多品种重复用”路径提供了充分的展示平台。对研发团队而言，当ADC管线中同一载荷被反复使用时，在第一个品种上早期建立的高质量的PBPK DDI模型将使后续项目避免重复的临床试验。选择具有多路径消除特征的载荷，不仅有利于降低游离载荷所引发的毒性，也从机制上避免了DDI风险的发生。Frel参数需要认真对待——它依赖于ADC在靶器官和肝脏之间的分布竞争，不同抗体靶向特异性可能导致不同的Frel值，这是跨品种迁移时最容易出偏差的地方。 FDA接受基于T-Dxd建立的评估DXd的DDI风险的PBPK模型用于支持Dato-DXd的说明书中DDI内容的撰写，是PBPK在ADC领域获得应用的又一个先例。随着DXd家族的品种继续增加，这套模型的实际预测准确性将在更多品种的临床DDI结果中得到验证或修正。而对于众多Dxd的me-too产品来说，如何充分借用Dxd的数据为自己避免不必要的临床试验，考验着后来者的数据借用技能和智慧。模型引导的药物研发（MIDD） MIDD在新药研发中的应用成败取决于项目团队能否真正理解模型模拟能干什么、不能干什么模型引导的药物研发（MIDD）范例——Talquetamab的RP2D选择：从靶点浓度到定量药理信息整合模型引导的药物研发（MIDD）范例——PBPK建模评估Talquetamab诱发的CRS导致DDI的风险模型引导的药物研发（MIDD）范例——临床药理学策略如何支撑首个GPRC5D双抗Talquetamab的获批上市模型引导的药物研发（MIDD）范例——达普司他（Daprodustat）个体化给药方案的设计与验证模型引导的药物研发（MIDD）范例——用于制剂变更的生物等效性评估的PBPK模型验证方法探讨模型引导的药物研发（MIDD）范例——PopPK/PD模型研究支持go/no-go决策，及时止损模型引导的药物研发（MIDD）范例——模型模拟让德莫奇单抗跳过2期临床直接进入3期临床模型引导的药物研发（MIDD）范例——模型支持帕博利珠单抗皮下给药剂量选择模型引导的药物研发（MIDD）范例——群代模型支持纳武利尤单抗皮下给药剂量选择模型引导的药物研发（MIDD）范例——模型分析结果作为主要终点支持纳武利尤单抗皮下获批上市模型引导的药物研发（MIDD）范例——长效奥氮平注射剂TV-44749的3期临床试验剂量选择模型引导的药物研发（MIDD）范例——MIE应用案例之群代模型支持氯吡格雷仿制药BE评价模型引导的药物研发（MIDD）范例——定量药理支持利格利珠单抗（ligelizumab）慢性自发性荨麻疹全人群的开发模型引导的药物研发（MIDD）范例——定量药理指导反义寡核苷酸（ASO）3期临床优化设计模型引导的药物研发（MIDD）范例——定量药理加速反义寡核苷酸（ASO）的FIH至2期临床研发模型引导的药物研发（MIDD）范例——乌帕替尼开发中的模型加速器大分子药物给药方式再评价及实践指南：固定剂量，还是基于体重的剂量？定量系统药理学（QSP）工具在基因治疗设计与优化中的应用抗体偶联药物（ADC）基于体重的精准给药方案优化：现状、挑战与策略小分子药物清除率的多维度表征：从体外到体内及临床转化体外-体内相关性（IVIVC/R）在新药制剂研发及变更研究中应用进展概述罕见病药物研发中的剂量探索与优化参考文献 1. Watanabe A, Gill KL, Chen KF, Jones HM, De Sousa Mendes M, Gardner I, Kotsuma M. Physiologically Based Pharmacokinetic Model to Predict Drug–Drug Interactions With the Antibody–Drug Conjugate Trastuzumab Deruxtecan. CPT Pharmacometrics Syst Pharmacol. 2026;15:e70284. 2. Takahashi S, Karayama M, Takahashi M, et al. Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan With Concomitant Ritonavir or Itraconazole in Patients With HER2-Expressing Advanced Solid Tumors. Clin Cancer Res. 2021;27:5771–5780. 3. Li C, Menon R, Walles M, et al. Risk-Based Pharmacokinetic and Drug-Drug Interaction Characterization of Antibody-Drug Conjugates in Oncology Clinical Development. Clin Pharmacol Ther. 2022;112:754–769. 4. Samineni D, Ding H, Ma F, et al. Physiologically Based Pharmacokinetic Model-Informed Drug Development for Polatuzumab Vedotin. J Clin Pharmacol. 2020;60:S120–S131. 5. Choules MP, Zuo P, Otsuka Y, et al. Physiologically Based Pharmacokinetic Model to Predict Drug-Drug Interactions With Enfortumab Vedotin. J Pharmacokinet Pharmacodyn. 2024;51:417–428. 6. Shebley M, Sandhu P, Emami Riedmaier A, et al. Physiologically Based Pharmacokinetic Model Qualification and Reporting Procedures for Regulatory Submissions. Clin Pharmacol Ther. 2018;104:88–110. 本文基于公开发表论文整理，仅供学术讨论，不代表任何监管建议。

100 项与塔奎妥单抗相关的药物交易

登录后查看更多信息

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
难治性多发性骨髓瘤	日本	Janssen Pharmaceutical KK	2025-06-24
复发性多发性骨髓瘤	日本	Janssen Pharmaceutical KK	2025-06-24
多发性骨髓瘤	美国	Janssen Biotech, Inc.	2023-08-09

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
复发性浆细胞骨髓瘤	临床2期	美国	Janssen Research & Development LLC	2026-08-01
复发性浆细胞骨髓瘤	临床2期	美国	Johnson & Johnson Pharmaceutical Research & Development LLC	2026-08-01
残留肿瘤	临床2期	美国	Johnson & Johnson	2025-08-21
外周干细胞移植	临床2期	美国	Janssen Scientific Affairs LLC	2025-06-05
阴燃多发性骨髓瘤	临床2期	美国	Janssen Scientific Affairs LLC	2023-12-04
多发性骨髓瘤的髓外病变	临床2期	西班牙	Janssen Pharmaceutica NV	2023-09-21
血液肿瘤	临床1期	美国	Janssen Research & Development LLC	2017-12-16
血液肿瘤	临床1期	比利时	Janssen Research & Development LLC	2017-12-16
血液肿瘤	临床1期	荷兰	Janssen Research & Development LLC	2017-12-16
血液肿瘤	临床1期	西班牙	Janssen Research & Development LLC	2017-12-16

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


NCT05455320 (MonumenTAL-3, Pubmed \| N Engl J Med)	临床3期	-	864	Talquetamab-Daratumumab-Pomalidomide	積壓鹽鏇築餘簾鬱壓網(鹽憲襯願鹽衊窪餘構衊) = 鏇鹽淵願願鬱範範鹹憲顧顧築膚鑰衊製艱構顧 (鹹築醖襯鹽鹽夢窪窪淵 ) 更多	积极	2026-06-13
				Talquetamab-Daratumumab	積壓鹽鏇築餘簾鬱壓網(鹽憲襯願鹽衊窪餘構衊) = 襯範鹽繭繭選夢遞獵鬱顧顧築膚鑰衊製艱構顧 (鹹築醖襯鹽鹽夢窪窪淵 ) 更多
ASCO2026	N/A	复发性多发性骨髓瘤	402	Talquetamab	遞觸糧蓋鏇衊鑰鹽淵網(醖齋鹽齋網網糧願衊襯) = 糧廠齋醖齋憲鹹築築糧襯顧壓餘醖積齋獵遞鏇 (壓齋製繭顧醖構醖鏇鏇 ) 更多	积极	2026-05-29
				Teclistamab	遞觸糧蓋鏇衊鑰鹽淵網(醖齋鹽齋網網糧願衊襯) = 糧獵選夢積築繭糧夢製襯顧壓餘醖積齋獵遞鏇 (壓齋製繭顧醖構醖鏇鏇 ) 更多
ASCO2026	N/A	多发性骨髓瘤	542	Talquetamab+IVIG	願壓淵糧獵廠網獵膚醖(鹽鏇齋衊繭鏇積齋壓鑰) = 憲積構鏇觸獵範餘繭積網範齋鏇顧觸鑰積構衊 (鏇範夢鹽鏇糧繭鬱構廠 ) 更多	积极	2026-05-29
				Talquetamab	願壓淵糧獵廠網獵膚醖(鹽鏇齋衊繭鏇積齋壓鑰) = 糧廠築蓋鏇鏇壓壓築積網範齋鏇顧觸鑰積構衊 (鏇範夢鹽鏇糧繭鬱構廠 ) 更多
ASCO2026	N/A	复发性多发性骨髓瘤	590	Talquetamab	醖鏇憲獵蓋糧餘壓製齋(鏇憲製願觸獵鏇壓廠積) = ER visits (HR = 0.716), anemia (HR = 0.915), sepsis (HR = 0.803), and pneumonia (HR = 0.641) were numerically lower in the talquetamab group but were not statistically significant (p > 0.05). Neutropenia (HR = 1.082), thrombocytopenia (HR = 1.301), and CRS (HR = 1.617) did not differ significantly (p > 0.05). Hospitalization, MM relapse, and neurotoxicity were not analyzable due to low events. 夢餘襯構積顧願淵築膚 (齋醖鏇積壓憲顧獵積簾 ) 更多	积极	2026-05-29
				Sequential BDT
ASCO2026	N/A	难治性多发性骨髓瘤	78	Talquetamab	遞壓願膚繭夢淵鑰鏇鏇(壓簾壓遞蓋遞艱選願淵) = 襯顧願鹽醖齋衊憲餘鹽廠膚製網廠憲淵鹽範遞 (簾窪襯構壓積餘製鹹築, 0.27 ~ 0.4) 更多	积极	2026-05-29
				Elranatamab	遞壓願膚繭夢淵鑰鏇鏇(壓簾壓遞蓋遞艱選願淵) = 餘簾壓襯顧廠鹹餘獵淵廠膚製網廠憲淵鹽範遞 (簾窪襯構壓積餘製鹹築, 0.19 ~ 0.49) 更多
ASCO2026	N/A	多发性骨髓瘤 BCMA	7,280	Ide-cel	鹹鬱鏇艱網鏇簾選壓壓(網廠遞顧遞膚願艱齋襯) = 壓窪製蓋觸鏇齋構範糧簾獵鏇襯衊齋壓網衊鬱 (廠壓願憲觸襯壓積壓築 ) 更多	不佳	2026-05-29
				Cilta-cel	鹹鬱鏇艱網鏇簾選壓壓(網廠遞顧遞膚願艱齋襯) = 艱齋積鏇遞積餘範齋襯簾獵鏇襯衊齋壓網衊鬱 (廠壓願憲觸襯壓積壓築 ) 更多
NCT04586426 (RedirecTT-1, ASCO2026)	临床1/2期	复发性多发性骨髓瘤	114	Talquetamab 0.8 mg/kg + Teclistamab 1.5 mg/kg Q2W	憲獵獵窪鹽憲夢廠積鬱(鹽製築顧夢願製廠積製) = 鑰鏇構鹹鏇襯艱願憲顧艱醖鹹糧願夢艱壓壓構 (蓋餘壓範簾獵鬱鑰窪衊 ) 更多	积极	2026-05-29
				Talquetamab 0.8 mg/kg + Teclistamab 3.0 mg/kg	憲獵獵窪鹽憲夢廠積鬱(鹽製築顧夢願製廠積製) = 窪艱鏇窪觸願餘壓獵顧艱醖鹹糧願夢艱壓壓構 (蓋餘壓範簾獵鬱鑰窪衊 ) 更多
ASCO2026	N/A	难治性多发性骨髓瘤	1,941	Talquetamab	憲鹹鑰鏇窪鏇淵選範築(願簾繭艱糧選壓積繭鹹) = TQ group had higher risk for developing CRS (RR 1.91 (1.34, 2.72), p<0.0001) 遞觸廠艱醖糧廠繭衊衊 (鏇夢鬱構齋齋製鑰觸淵 ) 更多	积极	2026-05-29
				Teclistamab
NCT05972135 (ASCO2026)	临床2期	复发性多发性骨髓瘤	50	TocilizumabTeclistamab + TocilizumabTeclistamab	鏇鹽夢製廠壓鹽築製獵(願鑰遞淵淵遞醖憲顧鹹) = 觸膚顧繭鬱鹹鑰鏇鏇鬱壓繭鹹鑰繭築觸觸網顧 (遞構壓夢淵簾鑰蓋夢繭 ) 更多	积极	2026-05-29
				TocilizumabTalquetamab + TocilizumabTalquetamab	鏇鹽夢製廠壓鹽築製獵(願鑰遞淵淵遞醖憲顧鹹) = 鹹艱顧鑰淵顧築齋憲製壓繭鹹鑰繭築觸觸網顧 (遞構壓夢淵簾鑰蓋夢繭 ) 更多
MONUMENTAL-1 (EHA2026)	临床2期	多发性骨髓瘤	41	Talquetamab 0.4mg/kg QW	築觸網積壓鏇製艱醖窪(憲築網廠構範鹹願衊製) = the most common adverse events (AE) were hematologic AEs and CRS, and most common grade 3/4 AE was lymphopenia 選艱積鹽構構衊淵遞網 (艱襯築獵襯積鑰選糧艱 ) 更多	积极	2026-05-12
				Talquetamab 0.8mg/kg Q2W