The purpose of this study is to is to determine the effects (good and bad) of Zanubrutinib in Combination with Pola-R-CHP and High-dose Methotrexate in patients with Secondary Central Nervous System (CNS) Lymphoma.

开始日期2025-03-31

申办/合作机构

University of Miami

[+1]

NCT06665217 / Not yet recruiting临床2期IIT

Glofitamab, Polatuzumab Vedotin, Zanubrutinib, Lenalidomide and Prednisone in Previously Untreated Diffuse Large B-Cell Lymphoma

The goal of this phase 2 trial is to test the safety and efficacy of G-Pola-ZLP as induction therapy in patients with DLBCL.

开始日期2025-01-01

申办/合作机构

海军总医院

NCT06664411 / Not yet recruiting临床2期IIT

Polatuzumab Vedotin, Zanubrutinib, Rituximab, Lenalidomide and Prednisone in Previously Untreated Diffuse Large B-Cell Lymphoma

The goal of this phase 2 trial is to test the safety and efficacy of Pola-ZR2P as induction therapy in patients with DLBCL.

开始日期2024-12-01

申办/合作机构

海军总医院

100 项与维泊妥珠单抗相关的临床结果

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100 项与维泊妥珠单抗相关的转化医学

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100 项与维泊妥珠单抗相关的专利（医药）

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196

项与维泊妥珠单抗相关的文献（医药）

2025-01-02·Expert Opinion On Drug Safety

A real-world pharmacovigilance analysis of the FDA adverse event reporting system events for polatuzumab vedotin

Article

作者: Liu, Sha ; Liu, Jiating ; Liu, Qiusha ; Wang, Hongli ; Shen, Zhengze ; Xu, Zhongliang ; Huang, Dan

BACKGROUND:

Polatuzumab vedotin is the first antibody-drug conjugate approved by the US Food and Drug Administration (FDA) for patients with diffuse large B-cell lymphoma. This study evaluated adverse events (AEs) associated with polatuzumab vedotin by data mining of the FDA Adverse Event Reporting System (FAERS).

METHODS:

This study included AEs registered in FAERS between 2019 Q2 and 2023 Q2. Four algorithms were used to quantify the signals of polatuzumab vedotin-associated AEs, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.

RESULTS:

A total of 7,609,450 reports were collected from the FAERS database, and 1,388 reports of polatuzumab vedotin were identified as primary suspected AEs. Polatuzumab vedotin-associated AEs involved 26 organ systems. According to the four algorithms, 108 significant disproportionality AEs were retained simultaneously. Unexpected significant AEs included gastrointestinal hemorrhage, ileus, gastrointestinal perforation, cholecystitis, hypogammaglobulinemia, hepatitis B reactivation, hypercalcemia, hydronephrosis, cystitis hemorrhagic, interstitial lung disease, and thrombophlebitis. The median time to onset of polatuzumab vedotin-associated AEs was 20 (interquartile range 4-56) days.

CONCLUSIONS:

Our study identified significant new AE signals for polatuzumab vedotin through real-world disproportionality analysis data and may provide additional evidence for risk identification of polatuzumab vedotin.

2025-01-01·HEMATOLOGICAL ONCOLOGY

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B‐Cell Lymphoma: A Real‐World, Multi‐Center, Retrospective Cohort Study

Article

作者: Xu, Junqing ; Wang, Jiesong ; Chen, Daoguang ; Qian, Zhengzi ; Zhao, Shu ; Li, Wei ; Zhou, Shiyong ; Liu, Xianming ; Li, Yajun ; Zhang, Qingyuan ; Zhao, Peiqi ; Zheng, Yanbin ; Chen, Ying ; Gao, Yuhuan ; Qiu, Lihua ; Zhang, Huilai ; Li, Lanfang ; Jiang, Yanan ; Zhou, Hui ; Huang, Chen

ABSTRACT:

Polatuzumab vedotin plus R‐CHP (Pola‐R‐CHP) is approved as a new standard first‐line therapy for diffuse large B‐cell lymphoma (DLBCL) based on the POLARIX trial. However, real‐world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola‐R‐CHP versus R‐CHOP outcomes in routine clinical practice in China. This is a multi‐institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola‐R‐CHP and 469 R‐CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow‐up of 12.8 months, 12‐month progression‐free survival (PFS) was numerically higher with Pola‐R‐CHP versus R‐CHOP (90.3% vs. 84.1%, p = 0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG ≥ 2, extranodal involvement ≥ 2 and non‐GCB group. The complete response rate of the Pola‐R‐CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p = 0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola‐R‐CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL‐6, KMT2D, SOCS1, BCL‐2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real‐world study supports Pola‐R‐CHP as an effective frontline option for DLBCL, with sustained efficacy versus R‐CHOP observed in unselected populations. While 12‐month PFS failed to reach statistical significance, subgroup analyses favor Pola‐R‐CHP. Further research with a wider population, longer follow‐up, and screening of advantageous groups are warranted.

2024-12-16·CLINICAL CANCER RESEARCH

FDA Approval Summary: Polatuzumab Vedotin in the First-Line Treatment of Select Large B-Cell Lymphomas

Article

作者: Sarraf Yazdy, Maryam ; Theoret, Marc R. ; Rodriguez, Lisa R. ; Gu, Wenjuan ; Bhatnagar, Vishal ; Pazdur, Richard ; Kasamon, Yvette L. ; Jin, Susan ; Richardson, Nicholas C. ; Gormley, Nicole J.

Abstract:

In April 2023, the U.S. FDA granted regular approval to polatuzumab vedotin-piiq in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (pola+R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma, not otherwise specified, or high-grade B-cell lymphoma and who have an International Prognostic Index score of 2 or greater. Approval was based on POLARIX, a randomized, double-blinded, placebo-controlled trial evaluating the superiority of substituting vincristine with polatuzumab vedotin in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen as first-line therapy for patients with large B-cell lymphoma. Efficacy was based on investigator-assessed progression-free survival (PFS) in 879 patients who were randomized to receive pola+R-CHP or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, followed by two cycles of rituximab alone. PFS was statistically significantly longer with pola+R-CHP, with an HR of 0.73 (95% confidence interval, 0.57–0.95) and log-rank P value of 0.0177 (two-sided α = 0.05). There was no improvement demonstrated in the key secondary endpoints of the complete response rate at the end of therapy or overall survival (OS). Several issues raised uncertainty about the benefit–risk profile of polatuzumab vedotin in this curative-intent setting, including the modest PFS benefit of pola+R-CHP and lack of OS benefit. The application was therefore presented at an Oncology Drugs Advisory Committee. This article summarizes key aspects of the regulatory review, including perspectives on PFS and OS results and other endpoints.

483

项与维泊妥珠单抗相关的新闻（医药）

2025-01-04

·ioncology

ASH看世界丨Gilles Salles教授：纪念斯隆凯特琳癌症中心淋巴瘤治疗优化探索

编者按 2024年12月7日至10日，第66届美国血液学会（ASH）年会在美国圣迭戈隆重召开，全球血液学专家学者齐聚一堂，共同对血液领域最新研究进展进行深入探讨与交流。《肿瘤瞭望-血液时讯》特邀纪念斯隆凯特琳癌症中心（MSK）Gilles Salles教授分享淋巴瘤领域的关键发现以及参会感受。 01 《肿瘤瞭望-血液时讯》首先请您简要介绍一下您的专业领域和研究方向？ Gilles Salles教授：大家好，我是纪念斯隆凯特琳癌症中心（MSK）的Gilles Salles博士。我始终专注于淋巴瘤治疗领域的研究，尤其深耕于B细胞淋巴瘤，涵盖了大B细胞淋巴瘤以及惰性淋巴瘤，如滤泡性淋巴瘤。当下，我们正处于淋巴瘤治疗极具突破性的时代。回顾过往，传统化疗或高剂量化疗模式逐渐被革新。25年前，利妥昔单抗的出现成为首个重大突破，开启了淋巴瘤治疗新篇章；随后，细胞疗法蓬勃兴起，CAR-T细胞疗法备受瞩目；时至今日，双特异性抗体又为治疗带来了新契机，这些创新药物都促使淋巴瘤治疗不断迈向新台阶，取得诸多实质性成果。与此同时，随着科研深入，我们对B细胞淋巴瘤的分子层面认知愈发深入，不同分子亚型得以精准区分，这为后续的个性化治疗奠定了基础，进而为B细胞淋巴瘤的亚型制定特定治疗方案。我和我的团队正在这些领域攻坚克难。以双特异性抗体为例，我们着力探索如何优化其临床应用，特别是针对滤泡性淋巴瘤患者。为进一步探索双特异性抗体的作用机制，我们开展了体外与体内试验。另外，大样本量患者的分子数据研究也在推进，旨在为患者提供更合适的治疗方案。尽管我们不能治愈所有患者，但不可否认，过往积累的诸多实质性的成果已让我们向前迈进一大步。这一伟大进程凝聚着全球淋巴瘤领域同仁的心血，无论他们身处美国、中国，还是世界其他角落，大家携手奋进，共同为攻克淋巴瘤难题不懈努力。（上下滑动查看英文原文） Oncology Frontier-Hematology Frontier：Could you please briefly introduce yourself, as well as your field and research directions? Dr. Gilles Salles：Hello everyone, I am Dr. Gilles Salles from Memorial Sloan Kettering Cancer Center (MSK). I have always been dedicated to research in the field of lymphoma treatment, with a particular focus on B-cell lymphomas, including diffuse large B-cell lymphoma and indolent lymphomas such as follicular lymphoma. Today, we are in an era of groundbreaking advancements in lymphoma treatment. Looking back, traditional chemotherapy or high-dose chemotherapy regimens have gradually been revolutionized. 25 years ago, the emergence of rituximab marked the first significant breakthrough, opening a new chapter in lymphoma treatment; subsequently, cellular therapies have flourished, with CAR-T cell therapy garnering considerable attention; now, bispecific antibodies have brought new opportunities for treatment, and these innovative drugs have continuously pushed lymphoma treatment to new levels, achieving many substantial outcomes. At the same time, with in-depth research, our understanding of the molecular aspects of B-cell lymphomas has become more profound, allowing for the precise differentiation of various molecular subtypes, which lays the foundation for subsequent personalized treatment and paves the way for specific treatment plans for subtypes of B-cell lymphoma. My team and I are tackling challenges in these areas. Taking bispecific antibodies as an example, we are focusing on exploring how to optimize their clinical application, especially for patients with follicular lymphoma. To further investigate the mechanisms of action of bispecific antibodies, we have conducted in vitro and in vivo experiments. Additionally, large-sample molecular data research on patients is also underway, aiming to provide more appropriate treatment plans. Although we cannot cure all patients, it is undeniable that the many substantial outcomes accumulated over the past have allowed us to take a significant step forward. This great process is the result of the efforts of colleagues in the global lymphoma field, whether they are in the United States, China, or other parts of the world, everyone is working together to make unremitting efforts to conquer the challenges of lymphoma. 02 《肿瘤瞭望-血液时讯》您能简要介绍一下在这次会议期间汇报的研究吗？ Gilles Salles教授：我们报告的这项POLARIX研究（NCT03274492），其方法曾于2022年发表在NEJM上。18-80岁患者以1:1的比例随机接受6个周期Pola-R-CHP或R-CHOP治疗，以及2个周期利妥昔单抗治疗。主要终点为PFS。我们此次报告了POLARIX研究的5年长期随访研究数据，探讨了与R-CHOP方案相比，维泊妥昔单抗+利妥昔单抗、环磷酰胺、多柔比星和泼尼松（Pola-R-CHP）治疗中高危弥漫性大B细胞淋巴瘤（DLBCL）患者的长期疗效。综上，POLARIX研究的5年随访结果显示，与接受R-CHOP治疗的患者相比，接受Pola-R-CHP治疗的患者PFS和DFS持续且显著获益。Pola-R-CHP组与R-CHOP组的OS均尚可，然而，R-CHOP组的（包括淋巴瘤相关死亡）死亡人数更多，且治疗的2年以上的死亡率更高。此外，两组之间的安全性特征持续相似，未观察到新的安全性信号，证实Pola-R-CHP作为中高危DLBCL患者标准一线治疗的疗效及安全性。中文标题：POLARIX研究的5年分析：延长随访证实维泊妥珠单抗联合利妥昔单抗、环磷酰胺、多柔比星和泼尼松（Pola-R-CHP）对临床疗效有积极影响英文标题：Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes 【滑动查看研究内容】摘要号：469 入组患者情况如下：在意向分析治疗（ITT）人群中，分别有879例患者（Pola-R-CHP组为440例，R-CHOP组为439例）和873例患者（Pola-R-CHP组为435例，R-CHOP组为438例）的数据可评估疗效和安全性。在扩展人群中，分别有1000例患者（Pola-R-CHP组为500例，R-CHOP组为500例）和993例患者（Pola-R-CHP组为495例，R-CHOP组为498例）的数据可评估疗效和安全性。在ITT人群中（中位随访时间60.9个月），Pola-R-CHP组和R-CHOP组的5年PFS率分别为64.2% vs. 59.1%，前者显示出显著获益（HR：0.78；95%CI：0.623-0.980）。Pola-R-CHP组和R-CHOP组的5年OS率估计值分别为82.2%（95%CI：78.53%-85.82%）vs. 79.6%（95%CI：75.70%-83.47%），与2年随访时的风险比（HR 0.94；95%CI：0.650-1.370）相比，5年随访时的风险比有所改善（HR：0.87；95%CI：0.641-1.175）。Pola-R-CHP组和R-CHOP组的5年无病生存（DFS）率分别为 71.3%（95%CI：65.46%-77.05%）vs. 65.5%（95%CI：59.45%-71.45%），（HR：0.75；95%CI：0.570-0.992）。在扩展人群中（中位随访时间60.5个月），观察到相似的5年PFS数据显著获益，Pola-R-CHP组和R-CHOP组的5年PFS率估计值分别为 63.1%（95%CI：57.90%-68.26%）vs. 59.1%（95%CI：54.07%-64.15%），（HR：0.81；95%CI：0.652-0.996）。Pola-R-CHP组和R-CHOP组接受后续淋巴瘤全身治疗的患者分别为106例（21%）vs. 145例（29%）。Pola-R-CHP组和R-CHOP组的5年OS率分别为82.2%（95%CI：78.78%-85.68%）vs. 79.0%（95%CI：75.24%-82.70%），（HR：0.84；95%CI：0.632-1.119），两者差异无统计学意义。Pola-R-CHP组和R-CHOP组的5年DFS率分别为69.4%（95%CI：63.78%-75.05%）vs. 65.1%（95%CI：59.30%-70.92%），（HR：0.81；95%CI：0.625-1.042）。在扩展人群可评估安全性的993例患者中，Pola-R-CHP组和R-CHOP组的3-5级不良事件（AE）发生率分别为62.6% vs. 60.8%。Pola-R-CHP组（n=5）比R-CHOP组（n=12）的继发性恶性肿瘤发生率更低。在长期随访期间，未观察到新的安全性信号。Pola-R-CHP组和R-CHOP组的新发严重AE发生率相似，分别为1.8%和2.2%。无新发周围神经病变患者。Pola-R-CHP组和R-CHOP组分别有4例（0.8%）和1例（0.2%）患者发生严重感染。在扩展人群中，Pola-R-CHP组与R-CHOP组相比，患者死亡人数更少（90 例 vs. 107 例）。Pola-R-CHP组和R-CHOP组的淋巴瘤相关死亡分别为46例 vs. 62例（前2年，32例 vs. 39例；2年以上，14例 vs. 23例）。Pola-R-CHP组和R-CHOP组的感染（7 例 vs. 11 例）、心血管疾病（4 例 vs. 5 例）、继发性恶性肿瘤导致死亡（7例 vs. 5例）的发生情况相似。在一项竞争风险分析中，以非淋巴瘤相关死亡（包括研究治疗导致的死亡）作为竞争事件，Pola-R-CHP组和R-CHOP 组的 5 年淋巴瘤相关死亡累积发生率分别为 9.1% vs. 12.2%。（上下滑动查看英文原文） Oncology Frontier-Hematology Frontier：And could you please briefly introduce the research presented during this kind of meeting? Dr. Gilles Salles：POLARIX (NCT03274492) methods were published in Tilly et al. NEJM 2022. Pts 18–80 years were randomized 1:1 to receive 6 cycles of Pola-R-CHP or R-CHOP, plus 2 cycles of rituximab. The primary endpoint was PFS. In this analysis, 1000 pts (expanded population) were evaluated; 879 pts (global ITT population) from the main study (enrolled Nov 2017–Jun 2019) and 121 pts from a Chinese extension cohort (enrolled Jul 2019–Dec 2020; Song et al. Blood 2023). Extended follow-up of efficacy and safety are described. A competing risk analysis assessed the risk of death from lymphoma vs other causes.we report outcomes after 5 years of follow-up (cut-off, 5 July 2024) In the global ITT population, 879 (Pola-R-CHP, n=440; R-CHOP, n=439) and 873 pts (Pola-R-CHP, n=435; R-CHOP, n=438) were evaluable for efficacy and safety, respectively. In the expanded population, 1000 (Pola-R-CHP, n=500; R-CHOP, n=500) and 993 pts (Pola-R-CHP, n=495; R-CHOP, n=498) were evaluable for efficacy and safety, respectively. In the global ITT population (median follow-up 60.9 months), the 5-year PFS estimates were 64.2% (95% CI: 58.78–69.53) vs 59.1% (95% CI: 53.87–64.40) with Pola-R-CHP vs R-CHOP, showing a significant benefit (HR 0.78; 95% CI: 0.623–0.980). The 5-year OS estimates were 82.2% (95% CI: 78.53–85.82) vs 79.6% (95% CI: 75.70–83.47) with Pola-R-CHP vs R-CHOP, with an improved HR (0.87; 95% CI: 0.641–1.175) compared with the 2-year follow-up HR (0.94; 95% CI: 0.650–1.370). The 5-year disease-free survival (DFS) estimates were 71.3% (95% CI: 65.46–77.05) vs 65.5% (95% CI: 59.45–71.45) with Pola-R-CHP vs R-CHOP (HR 0.75; 95% CI: 0.570–0.992). In the expanded population (median follow-up 60.5 months), a similar significant 5-year PFS benefit was observed, with estimates of 63.1% (95% CI: 57.90–68.26) vs 59.1% (95% CI: 54.07–64.15) with Pola-R-CHP vs R-CHOP (HR 0.81; 95% CI: 0.652–0.996). The number of pts requiring subsequent systemic lymphoma therapy was 106 (21%) vs 145 (29%) with Pola-R-CHP vs R-CHOP. The 5-year OS estimates were 82.2% (95% CI: 78.78–85.68) vs 79.0% (95% CI: 75.24–82.70) with Pola-R-CHP vs R-CHOP, with no statistically significant difference (HR 0.84; 95% CI: 0.632–1.119). The 5-year DFS estimates were 69.4% (95% CI: 63.78–75.05) vs 65.1% (95% CI: 59.30–70.92) with Pola-R-CHP vs R-CHOP (HR 0.81; 95% CI: 0.625–1.042). Safety profiles were comparable with Pola-R-CHP vs R-CHOP across all safety-evaluable pts in the expanded population (n=993), including Grade 3–5 AE rates (62.6% vs 60.8%). Fewer secondary malignancies were observed with Pola-R-CHP (n=5) vs R-CHOP (n=12). No new safety signals were observed during long-term follow-up; similar rates of new serious AEs were reported with Pola-R-CHP and R-CHOP (1.8% and 2.2%, respectively). No new cases of peripheral neuropathy were reported. Serious infections occurred in 4 pts (0.8%) vs 1 (0.2%) pt with Pola-R-CHP vs R-CHOP. In the expanded population, fewer total deaths were observed in pts treated with Pola-R-CHP vs R-CHOP (90 vs 107). Lymphoma-related deaths occurred in 46 vs 62 pts with Pola-R-CHP vs R-CHOP (during the first 2 years, 32 vs 39 pts; beyond 2 years, 14 vs 23 pts for Pola-R-CHP vs R-CHOP). Similar numbers of deaths from infection (7 vs 11), cardiovascular disease (4 vs 5), and secondary malignancy (7 vs 5) were observed with Pola-R-CHP vs R-CHOP. In a competing risk analysis, with non-lymphoma-related deaths (including death due to study treatment) as competing events, the cumulative incidence of lymphoma-related death at 5 years was 9.1% vs 12.2% for Pola-R-CHP vs R-CHOP. In summary，extended 5-year follow-up of POLARIX demonstrated sustained and significant PFS and DFS benefits for pts receiving Pola-R-CHP vs R-CHOP. OS was reassuring between pts with Pola-R-CHP and R-CHOP, with more deaths, including lymphoma-related deaths, observed with R-CHOP. With the observation that a higher proportion of pts receiving R-CHOP died beyond 2 years, prolonged follow-up will be of interest. Safety profiles remained similar between arms, and no new safety signals were identified. These outcomes confirm Pola-R-CHP as a standard of care for pts with previously untreated intermediate- or high-risk DLBCL 03 《肿瘤瞭望-血液时讯》您认为此次会议哪些重要进展或突破性研究值得关注？这些发展可能会如何影响临床诊断和治疗？ Gilles Salles教授：在淋巴瘤相关研究领域，诸多杰出成果不断涌现。中国学者运用前沿的成像质谱流式技术取得了重大突破，一方面，针对 EBV+DLBCL展开深入探究，全方位阐释了其具有免疫抑制特性的微环境，并且精准剖析出引发该免疫抑制性微环境的内在调控机理（摘要号：452）；另一方面，还发现了肿瘤免疫微环境（TIME）在滤泡性淋巴瘤（FL）的早期进展历程中扮演着举足轻重的角色（摘要号：1621）。与此同时，在免疫疗法的优化探索上也有新进展。生酮饮食这一干预手段被证实可通过 β- 羟基丁酸来强化 CAR-T 细胞的抗肿瘤功能（摘要号：4）。综合这些前沿发现来看，无论是当下的淋巴瘤治疗实践，还是面向未来的免疫疗法研发，均存在着诸多可拓展的领域与创新方法，有望助力免疫疗法实现质的飞跃。这些研究成果必然会对淋巴瘤治疗产生深远影响。在诊断层面，随着技术发展，分子分类得以持续优化，如今已能够依据患者的分子特征，更为精准、有针对性地筛选合适药物，进而提升治疗的精准度与有效性，为淋巴瘤患者带来更多治愈希望。（上下滑动查看英文原文） Oncology Frontier-Hematology Frontier：And during this meeting, what are the significant advancements or groundbreaking research presented at this conference that you think deserve attention?And how might those developments impact clinical diagnosis and treatment? Dr. Gilles Salles：In the field of lymphoma-related research, numerous outstanding achievements continue to emerge. Chinese scholars have made significant breakthroughs using cutting-edge imaging mass cytometry technology. On one hand, they have conducted in-depth studies on EBV+DLBCL, comprehensively elucidating its microenvironment with immune-suppressive characteristics and precisely dissecting the internal regulatory mechanisms that lead to this immune-suppressive microenvironment (Abstract No.: 452). On the other hand, they have also discovered that the tumor immune microenvironment (TIME) plays a pivotal role in the early progression of follicular lymphoma (FL) (Abstract No.: 1621). At the same time, there have been new developments in the optimization of immunotherapy. The ketogenic diet, as an intervention measure, has been proven to enhance the anti-tumor function of CAR-T cells through β-hydroxybutyrate (Abstract No.: 4). Integrating these cutting-edge findings, there are many expandable fields and innovative methods in both current lymphoma immunotherapy practices and future immunotherapy research and development, which are expected to help immunotherapy achieve a qualitative leap. These research outcomes will undoubtedly have a profound impact on lymphoma treatment. In terms of diagnosis, with technological advancements, molecular classification continues to be optimized. Now, it is possible to select appropriate drugs more accurately and specifically based on the molecular characteristics of patients, thereby enhancing the precision and effectiveness of treatment and bringing more hope for cure to lymphoma patients. 04 《肿瘤瞭望-血液时讯》通过这次会议，您获得了哪些见解，这些见解将如何影响您的临床实践和未来的研究方向？ Gilles Salles教授：ASH会议为我们提供了与世界专家学者交流最新研究成果、探讨行业发展趋势的机会。我们在CAR-T细胞治疗领域收获颇多，并学习到了如何把临床试验结果转化为实践应用。新型药物如同雨后春笋不断涌现，极大地促进了我们对疾病的深入理解。这些进步不仅为患者群体带来了直接的益处，而且对整个医疗行业产生了深远的影响。（上下滑动查看英文原文） Oncology Frontier-Hematology Frontier：And through this meeting, what might be some insights you've gained, and how will those insights influence your clinical practice and future research directions? Dr. Gilles Salles：The ASH conference provides us with the opportunity to exchange the latest research findings with experts and scholars from around the world and to discuss industry trends. We have gained a lot in the field of CAR-T cell therapy and learned how to translate clinical trial results into practical applications. New drugs are emerging like mushrooms after rain, greatly promoting our in-depth understanding of diseases. These advancements have not only brought direct benefits to patient groups but also had a profound impact on the entire medical industry. （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。

细胞疗法免疫疗法ASH会议临床研究

2025-01-03

·小药说药

ADC的联合治疗

关注小药说药，一起成长！前言抗体偶联药物(ADC)是由靶向特异性抗原的单克隆抗体与小分子细胞毒性药物通过连接子链接而成,兼具传统小分子化疗的强大杀伤效应及抗体药物的肿瘤靶向性。ADC由三个主要部分组成：负责选择性识别癌细胞表面抗原的抗体，负责杀死癌细胞的药物有效载荷，以及连接抗体和有效载荷的连接子。 ADC目前已成为治疗血液恶性肿瘤和实体瘤的一类热门药物，进行了广泛的临床前和临床研究。然而，与大多数细胞毒性药物的情况一样，由于耐药机制的出现，ADC作为单一疗法产生的客观反应或临床益处的持续时间仍然受到限制。因此，ADC与其他抗癌药物的组合成为ADC药物开发的一个重要方向。目前，监管部门已批准了针对血液肿瘤的ADC与化疗/化学免疫治疗的组合，FDA也授予了enfortumab vedotin和pembrolizumab的突破性疗法认定。与ADCs组合最有吸引力的药物是那些对肿瘤细胞或其微环境具有加成或协同作用而没有不可接受的重叠毒性的合作伙伴。包括抗血管生成药物、HER2靶向药物、DNA损伤应答剂和免疫检查点抑制剂（ICIs）的联合用药是目前积极研究的方向。 ADC联合化疗 ADC与化疗药物的最佳组合需要更好地理解独特的细胞周期相互作用以及细胞毒性伴侣对表面抗原表达的调节。到目前为止，越来越多的临床前和临床数据显示出良好的应用前景，并为指导进一步的药物开发提供了宝贵的见解。细胞周期相互作用作用于S期并产生G2/M期阻滞的DNA损伤剂（例如抗代谢药物、铂和拓扑异构酶抑制剂）可与微管抑制剂组合。卡铂与mirvetuximab soravtansine、anetumab ravtanine或luveltamab tazevibulin在卵巢癌模型中的成功组合，说明了这一概念。在早期临床试验中，以ravtansine为基础的ADCs与卡铂或阿霉素联合治疗对铂敏感和耐药的卵巢癌患者，以及以deruxtecan为基础的ADCs与卡培他滨或顺铂联合治疗胃癌和肺癌患者的疗效显著。给药时间的设计给药时间可能与药物组合设计相关。微管蛋白聚合是ADC内吞机制的关键组成部分，DNA损伤介导的G2/M期阻滞可能需要一些时间让微管破坏物敏化发生。在结肠癌、肺癌和乳腺癌模型中的研究很好地证明了这一点，连续给药SGN-15（Lewis Y抗原- doxorubicin）和紫杉醇比同时给药引起更多的DNA碎片。这一观察表明，调整给药时间，特别是抗微管药物之后延迟给与DNA损伤剂，可能会提高治疗效果。表面抗原的调节化疗药物可以调节ADC靶向的表面抗原的表达。在这方面，吉西他滨已被证明可以上调胰腺腺癌细胞中HER2的表达，其中吉西他宾和trastuzumab emtansine的组合发挥了增强的效力。与上述细胞周期相互作用交织在一起，HER2上调尤其发生在G2/M群体中，这是吉西他滨介导的DNA合成抑制的结果。重叠毒性 ADC本质上是化疗，因此联合方案的疗效提高往往会受到不可接受毒性的阻碍。主要毒性由细胞毒性有效载荷代谢产物驱动，在设计组合策略时必须仔细考虑。这些毒性包括MMAE和DM1衍生物引起的周围神经病变、MMAF和DM4引起的眼毒性、DM1或拓扑异构酶抑制剂的胃肠道效应、或calicheamicin衍生物引起的肝毒性，以及几乎普遍的中性粒细胞减少症和血小板减少症。两项2a/b期研究证明了这一点，这两项研究调查了trastuzumab emtansine与多西紫杉醇或紫杉醇联合治疗HER2+晚期乳腺癌症，其中一半以上的患者需要减少剂量或停止紫杉烷。新的、更具肿瘤选择性的ADC药物，如mirvetuximab soravtansine和datotomab deruxtecan显示出更温和的毒性，使其成为具有不同作用机制的化疗药物的理想伴侣。 ADC联合靶向药物与标准化疗相比，ADC的治疗指数有所提高，对选择性肿瘤群体的活性也有所提高，这使其成为靶向药物的理想合作伙伴。人们可以设想各种组合策略，以克服治疗耐药性和克隆异质性，引发对癌基因依赖性信号通路的更强抑制，增加表面抗原的可用性并使低抗原表达肿瘤敏感，调节肿瘤微环境。用ADC替代化疗到目前为止，许多研究试图用ADC替代标准化疗，作为靶向药物的组合，但结果令人失望。KAITLIN、KRISTINE和MARIANNE等临床试验是基于与trastuzumab emtansine联合pertuzumab的协同抗肿瘤活性而设计的，然而在新辅助和转移环境中，与紫杉醇、曲妥珠珠单抗和帕妥珠珠单抗相比，其并没有显示出增强的疗效。同样，在卵巢癌中，联合贝伐单抗，anetumab ravtansine的疗效低于紫杉醇。酪氨酸激酶抑制剂（TKIs）通过添加TKI的双靶点阻断可以提供更大的选择性，并可能改善治疗指数。在TEAL研究中，与标准的紫杉醇、trastuzumab和pertuzumab联合用药相比，trastuzumab emtansine、泛-HER2抑制剂lapatinib和白蛋白结合性紫杉醇联合用药在HER2+乳腺癌患者的新辅助治疗中的反应有所改善Trastuzumab emtansine和tucatinib（一种更具选择性的抗HER2 TKI）的组合，在既往紫杉烷和trastuzumab治疗后进展的晚期患者中实现了47%的客观应答率（ORR），包括脑转移患者中36%的脑特异性应答率。新一代ADC和TKI可能会获得更好的结果。靶向ADC耐药越来越多的证据支持靶向药物可以同时靶向已知的ADC耐药机制。例如，由于HER2对乳腺上皮细胞的恶性转化依赖于细胞周期蛋白D1，CDK4/6抑制剂已在HER2耐药患者中与trastuzumab emtansine联合使用。此外，另一种关键的细胞周期调节因子PLK1最近被确定为获得性和原发性trastuzumab emtansine耐药模型中的上调靶点，其抑制剂volasertib可使trastuzumab emtansine在体外和体内再增敏。另一方面，ADC也可能是调节靶向药物耐药机制的有效组合。例如，osimertinib和trastuzumab emtansine的联合用药产生了额外的抗肿瘤作用，其中trastuzumab emtansine能够延迟或克服EGFR突变非小细胞肺癌模型中osimertinib的耐药性。表面抗原的调节一些TKI已被证明可调节表面抗原，可能促进进一步的ADC活性，并使低抗原表达肿瘤敏感。在这方面，lapatinib, neratinib, tucatinib, 和poziotinib已被证明可提高trastuzumab emtansine的疗效。然而，具体的机制原理仍不明确。其中lapatinib通过强烈的转录上调和减少泛素化增加HER2丰度，neratinib通过刺激内化和内吞作用降低表面HER2丰度，tucatinib对细胞表面HER2的影响仍然难以捉摸，而poziotinib上调外显子20突变，但不上调野生型HER2，这表明协同机制与表面HER2密度无关。抗血管生成抗血管生成剂可促进ADC穿透和肿瘤细胞暴露。anetumab ravtansine或mirvetuximab soravansine与贝伐单抗在卵巢癌症临床前模型中的联合应用具有完全响应的有效性。最近的一项1b期研究将mirvetuximab soravtansine和贝伐单抗联合用于重度预处理、铂耐药、FRα高的卵巢癌症患者，其中39%的ORR超过了关键AURELIA试验的基准值（27%）。 DNA损伤反应剂通过将靶向DNA损伤反应（DDR）的药物与携带DNA损伤剂的ADC相结合来开发合成致死，可能是治疗基因组不稳定肿瘤的一种有前途的策略。传统上，DDR药物与化疗的结合受到无法耐受毒性的阻碍，而携带拓扑异构酶I抑制剂有效载荷的新一代ADC的优越活性和耐受性使其更适合作为搭档。多个临床试验正在探索这一策略，包括niraparib和trastuzumab duocarmazine、talazoparib和sacituzumab govitecan，以及olaparib和trastuzumab deruxtecan。除了PARP抑制外，ADC对化疗的选择性增加无疑将扩大可组合DDR药物的范围，例如，ATR抑制剂berzosertib联合sacituzumab govitecan的临床实验目前正在进行中（NCT04826341）。 ADC联合免疫疗法免疫疗法和ADC的组合策略最近已进入临床实验。尽管临床前数据和早期临床研究的结果表明抗肿瘤活性增强，但支持该方法优于标准治疗的随机临床试验结果仍在等待中。抗PD-1/PD-L1和抗CTLA-4抗体越来越多的证据表明，ADC可能会提高免疫治疗剂的疗效。所涉及的机制是多种多样的，以及增强免疫记忆和免疫调节蛋白（如PD-L1和MHC）的表达。一些ADC在具有完整免疫系统的临床前模型中表现出更大的效力，支持其免疫调节功能的相关性。多种HER2靶向ADC，包括trastuzumab emtansine, trastuzumab deruxtecan和disitamab vedotin,已在体外和体内与ICI联合测试，证实了与增强的归巢和免疫效应物激活相关的协同活性。KATE2研究是唯一一项公开发表的检测ADC加ICI的随机试验，该研究比较了预治疗HER2+乳腺癌患者中trastuzumab emtansine联合atezolizumab对比trastuzumab emtansine联合安慰剂的疗效。联合治疗未能改善无进展生存期（8.2 vs 6.2个月，P=0.33），表明在HER2靶向治疗同时添加ICI可能仅对PD-L1阳性人群有益。尽管在这项随机试验中观察到令人失望的结果，但在多种肿瘤中临床探索仍在进行。此外，越来越多的临床前证据表明，组合疗法可能会恢复免疫敏感性。例如，在ICI难治性黑色素瘤和非小细胞肺癌（NSCLC）患者模型中，AXL特异性ADC enapotamab vedotin与抗PD-1抗体联合进行了测试，其中ADC通过诱导T细胞浸润和增强抗原提呈，增强了ICI活性并导致TME中的促炎性变化。 ADC联合其他免疫疗法 Polatuzumab vedotin已被证明通过增加AKT和ERK信号增强肿瘤细胞上CD20的表达，支持其与抗CD20抗体（例如利妥昔单抗）和CD20/CD3双特异性抗体疗法的联合。此外，ADC和免疫调节剂的组合也正在其他疾病中探索，如多发性骨髓瘤。在临床前模型中，belantamab mafodotin与OX40激动剂的组合产生了协同抗肿瘤活性，增加了肿瘤内T细胞和树突状细胞的浸润和活化。临床上正在积极研究belantamab mafodotin的组合方案，如DREAMM-5研究（NCT04126200），该研究与多种免疫治疗剂包括（抗ICOS抗体、OX40激动剂以及γ-分泌酶抑制剂）以及抗PD-1抗体联合给药。初步结果表明，联合抗ICOS抗体在重度预处理患者中具有良好的活性。此外，ADC的设计不仅可以针对癌症细胞，还可以调节TME的元素，如免疫细胞或成纤维细胞，从而改变免疫反应性。例如，靶向CD73的ADC显示出令人鼓舞的临床前活性。此外，在临床前模型中与pembrolizumab联合使用时，靶向癌相关成纤维细胞的ADC显示出增强CD8+T细胞介导的抗肿瘤活性。小结作为单药的ADC已证明具有抗肿瘤功效，并在多种实体瘤和血液瘤中获得了批准。学术界和工业界目前正在进行广泛的努力，通过确定新的靶点和增强其药理作用来开发下一代ADC，以及基于目前ADC的联合疗法。然而迄今为止，使用第一代和第二代ADC的组合方法成功有限，这可能归因于几个因素，例如靶点的非特异性表达导致正常组织中的不良反应、重叠毒性、不同肿瘤克隆中的疗效不足以及新出现的抗药性机制。因此，需要深刻了解ADC的药理学以及相关的预测性生物标记物组合，在特征良好的患者衍生异种移植模型中进行临床前评估，从而选择最有前途的基于ADC的组合。相信未来基于ADC的联合疗法将展现出光明的前景。参考文献： 1.Antibody-drug conjugates: in search of partners of choice. Trends Cancer.2023 Feb 4 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

抗体药物偶联物突破性疗法临床结果临床研究

2024-12-23

·美通社

罗氏又一款CD20/CD3双特异性抗体中国获批，T细胞疗法将给复发难治性滤泡性淋巴瘤带来临床新选择

上海 2024年12月23日 /美通社/ -- 2024年12月23日，罗氏制药中国宣布，中国国家药品监督管理局（NMPA）正式批准皓罗华 ® （英文商品名：Lunsumio ® ，中英文通用名：莫妥珠单抗/mosunetuzumab）单药用于治疗既往接受过至少两线系统性治疗的复发或难治性滤泡性淋巴瘤成人患者。作为全球首款 [1] 获批用于滤泡性淋巴瘤（FL）治疗的CD20/CD3双特异性抗体（以下简称"双抗"），莫妥珠单抗是继格菲妥单抗之后，罗氏在中国连续第二年获批的第二款CD20/CD3双抗药物。区别于格菲妥单抗独特的2:1结构，莫妥珠单抗是典型的1:1结构，两款结构不同的双抗分别覆盖不同的淋巴瘤亚型，给不同分型的淋巴瘤患者带来获益。治疗持久战：滤泡性淋巴瘤复发困局待解滤泡性淋巴瘤是非霍奇金淋巴瘤（NHL）中最常见的惰性亚型之一，我国滤泡性淋巴瘤的发病率占B细胞NHL的8%~23% [2] 。近年来，随着中国老龄化程度的增加，滤泡性淋巴瘤发病率也呈逐年上升的趋势 [3] 。目前滤泡性淋巴瘤仍是一种无法治愈的疾病，大多数患者会经历反复复发、进展，严重影响着患者的生存和生活质量。约有20%的患者接受免疫化疗后24个月内发生疾病进展（POD24） [4] ，随着复发次数的增加，后续治疗难度也不断升级，患者的缓解时间和生存时间也会缩短。滤泡性淋巴瘤患者因为疾病易复发、难治愈的特点长期承受着身心压力，影响生存质量。《2020中国滤泡性淋巴瘤患者生存状况白皮书》（下文简称《白皮书》）调查显示，滤泡性淋巴瘤患者深受疾病需要反复治疗的困扰，怀有对复发的恐惧，复发患者感受到更多的疼痛、焦虑、沮丧，生活质量远低于普通人群，绝大多数受访患者均表示对治疗滤泡性淋巴瘤的新药有非常迫切的需求 [5] 。进一步减少复发，获得更长时间和更高质量的生存是滤泡性淋巴瘤患者最为迫切的希望。哈尔滨血液病肿瘤研究所所长马军教授谈到："近年来淋巴瘤的治疗发展迅速，各类新型疗法和药物不断涌现，患者的生存状况得到了显著改善。然而，对于以滤泡性淋巴瘤为代表的惰性淋巴瘤而言，临床上仍存在巨大的未尽之需。虽然FL临床进展较为缓慢，病程较长，但临床治疗中约20%的患者可发生早期进展，这部分患者5年总生存（OS）率仅50%，死亡风险是非POD24患者的6到7倍。除早期进展，在一次次疾病复发的过程中，每年可能有2-3%的滤泡性淋巴瘤患者转化为其它侵袭性更强的淋巴瘤类型，这使得治疗变得更加复杂和困难，患者的生存期也随之缩短。" 改写复发或难治性滤泡性淋巴瘤治疗格局，莫妥珠单抗带来治疗新选择近年来，T细胞介导的免疫疗法在血液肿瘤治疗领域持续展现出巨大潜力，双特异性抗体是近年来最受关注的T细胞免疫疗法的一个研究方向，为传统治疗手段疗效不佳的患者带来了新的治疗选择 [5] 。由于滤泡性淋巴瘤具有高度异质性，分类复杂、诊断困难，需要为每个患者制定个体化的治疗方案，因此推动其规范化诊疗发展，让患者得到及时、有效的诊治就显得至关重要。"传统治疗的客观缓解率（ORR）和完全缓解（CR）率相对较低，复发或难治性滤泡性淋巴瘤患者一旦再次复发，会迫切需要创新疗法，T细胞介导的免疫疗法是我们学界关注的重点，我们临床中不断证实了双抗对于淋巴瘤后线患者治疗获益。" 苏州大学附属第一医院血液科主任吴德沛教授说道。莫妥珠单抗是IgG1样人源化双特异性抗体，能够同时靶向B细胞表面的CD20抗原和T细胞表面的CD3抗原，重定向T细胞并清除恶性B细胞。此次莫妥珠单抗中国获批是基于多中心、开放标签I/II期GO29781研究的积极结果。该研究旨在评估固定疗程莫妥珠单抗对既往接受两种或两种以上治疗的复发或难治性滤泡性淋巴瘤（R/R FL）患者的安全性和抗肿瘤活性。 GO29781研究的关键结果显示，患者的客观缓解率（ORR）为80%，完全缓释率（CR）为60%。高危POD24亚组的CR率为60%，与总体人群一致。最常见的不良事件（AE）为细胞因子释放综合征（CRS），主要为低级别（1-2级），中位随访37.4个月时，患者的3年OS率为82.4% [6] 。2024年CSCO大会上公布的数据显示，莫妥珠单抗在中国患者中的ORR高达88.2%，CR率为64.7%，与GO29781研究相符 [7] 。北京大学肿瘤医院党委书记朱军教授表示："如何延长滤泡性淋巴瘤患者的无病生存时间，改善复发或难治性患者预后，实现高质量长期生存仍是目前亟待攻破的难题。GO29781研究成果令人惊喜。我们中心入组患者情况与总体研究结果一致，经长期随访，使用莫妥珠单抗的患者获得了较高的完全缓解率，显著延长患者总生存期，且未在研究期间观察到严重不良事件的发生，证实了莫妥珠单抗在高效抗肿瘤的同时耐受性佳、安全性良好。更令人欣喜的是，我们观察到POD24患者同样能获得持久缓解和PFS获益，且越早使用莫妥珠单抗的患者能有更好的生存获益。"基于研究，莫妥珠单抗此前已在美国和欧盟获批，并被纳入2024年版《CSCO淋巴瘤诊疗指南》，推荐其用于复发或难治性滤泡性淋巴瘤（FL1~3a级）的治疗（II级推荐，2A类）。上海交通大学医学院附属瑞金医院副院长赵维莅教授表示："试验结果清晰展现，莫妥珠单抗不仅能够为复发或难治性滤泡性淋巴瘤患者带来长期生存获益，同时作为无需定制的即用型免疫疗法，莫妥珠单抗也为患者带来了门诊固定周期的全新治疗选择。结合中国临床现状，需要治疗的患者远比实际入院的患者多，莫妥珠单抗能够为因各种现实因素限制无法住院的患者提供了更为灵活、便利的用药场景和便捷的治疗体验，也为日后复发或难治性滤泡性淋巴瘤患者的规范化诊疗提供了新的可能。" 群星璀璨，罗氏引领中国血液疾病诊疗作为双抗研发领域的先行者，罗氏血液领域的第一个双特异性单克隆抗体艾美赛珠单抗于2019年进入中国，填补了A型血友病抑制物患者预防治疗的临床空白，作为非因子预防治疗创新疗法让A型血友病患者实现"零"出血 [8] 。在血液研发以外，罗氏已陆续布局多个双抗技术平台，将双抗技术应用到更多领域，全球首个眼科双抗药物 [9] 法瑞西单抗也已在中国获批多个适应症。罗氏全球药品开发中国中心负责人厉文泓："罗氏血液研发始终关注患者最迫切的需求，此次获批的莫妥珠单抗正是我们以创新研发满足患者治疗需求的又一力证。作为全球双抗研发领域的先行者，罗氏通过不同的技术平台，将产品差异化定位深植于分子设计，为患者带来多个具有独特临床价值的双抗治疗解决方案。未来，我们将继续专注研发，不断突破创新，为中国患者提供更加多元化的血液疾病创新产品。" 罗氏制药中国总裁边欣："在过去的四年时间里，皓罗华是继佳罗华、优罗华、高罗华之后罗氏给中国带来的第四款血液肿瘤创新药。如皓字含义一般，我们希望皓罗华如‘红日初升，其道大光'，给更多惰性淋巴瘤患者带来新的治疗选择。秉承‘先患者之需而行'的理念，罗氏将持续携手各个生态圈伙伴，科研助力学科发展，开创患者服务新模式，共同携手为中国血液肿瘤患者治愈而努力，坚定实践‘健康中国2030'宏伟蓝图。" [1] Cao, Y., Marcucci, E. C., & Budde, L. E. (2023). Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Journal of Hematology & Oncology, 16(69). https://doi-org.libproxy1.nus.edu.sg/10.1186/s13045-023-01462-0 [2] 中国抗癌协会血液肿瘤专业委员会, 中华医学会血液学分会淋巴细胞疾病学组, 中国滤泡淋巴瘤工作组, et al. 中国滤泡性淋巴瘤诊断与治疗指南（2023年版） [J]. 中华血液学杂志, 2023, 44(7): 529-34. [3] 中国抗癌协会淋巴瘤专业委员会、中华医学会血液学分会，中国滤泡性淋巴瘤诊断与治疗指南（2020年版） [4] Casulo C, Byrtek M, Dawson KL,et al. Early relapse of follicular lymphoma after rituximab pluscyclophosphamide, doxorubicin, vincristine, and prednisone defines patients athigh risk for death: an analysis from the National LymphoCare Study [correctionpublished in J Clin Oncol. 2016;34(12):1430]. J Clin Oncol. 2015;33(23):2516-2522. [5] 《2020中国滤泡性淋巴瘤患者生存白皮书》 [6] Stephen J. Schuster, et al., ASH 2023. oral 603. [7] LI Z , SHIYONG; LIU, YANYAN, et al. Safety and efficacy of mosunetuzumab monotherapy in Chinese patients with relapsed or refractory follicular lymphoma [J]. 2024 CSCO, 2024. [8] Callaghan, Michael U et al. "Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies." Blood vol. 137,16 (2021): 2231-2242. [9] Faricimab is the first bispecific antibody designed for intraocular use. In January 2022 faricimab received its first approvals（Drugs (2022) 82:825–830 https://doi-org.libproxy1.nus.edu.sg/10.1007/s40265-022-01713-3）

细胞疗法免疫疗法上市批准

100 项与维泊妥珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	维泊妥珠单抗	L01XC	DB12240

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
难治性淋巴瘤	加拿大	Hoffmann-La Roche Ltd.	2020-07-09
弥漫性大B细胞淋巴瘤	美国	Genentech, Inc.	2019-06-10

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性侵袭性非霍奇金淋巴瘤	临床3期	美国	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	中国	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	日本	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	阿根廷	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	巴西	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	加拿大	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	以色列	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	墨西哥	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	新西兰	Hoffmann-La Roche, Inc.	2022-04-25
难治性侵袭性非霍奇金淋巴瘤	临床3期	秘鲁	Hoffmann-La Roche, Inc.	2022-04-25

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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


ASH2024 人工标引	临床1期	弥漫性大B细胞淋巴瘤	22	Polatuzumab Vedotin+Zanubrutinib+Rituximab+Lenalidomide	艱糧觸夢遞構窪鏇製憲(構簾築鹽齋鬱顧衊願繭) = 獵觸鑰襯襯繭觸窪廠觸願遞糧艱糧觸餘鏇餘膚 (夢顧窪鑰憲膚鏇蓋餘醖 ) 更多	积极	2024-12-09
ASH2024	N/A	-	-	Pola-R-CHP	製餘鑰願鹽鹽艱艱餘淵(壓衊鹹憲積醖糧衊顧淵) = 願蓋衊夢憲網鹹夢艱願襯餘製簾鑰衊製鬱醖選 (觸醖簾鹹鑰淵餘蓋鑰製, 65.46 ~ 77.05) 更多	-	2024-12-08
ASH2024	N/A	-	-	R-CHOP	製餘鑰願鹽鹽艱艱餘淵(壓衊鹹憲積醖糧衊顧淵) = 獵顧築獵構壓醖簾積膚襯餘製簾鑰衊製鬱醖選 (觸醖簾鹹鑰淵餘蓋鑰製, 59.45 ~ 71.45) 更多	-	2024-12-08
SOHO2024	N/A	大B细胞淋巴瘤	-	Mosunetuzumab with Polatuzumab Vedotin	鏇積醖壓範鏇餘憲壓遞(築鏇網餘鬱鏇醖餘蓋艱) = 積選淵範糧選築遞繭觸範壓鏇齋鬱窪範鑰憲襯 (窪網齋淵鑰窪蓋選鑰積 ) 更多	-	2024-09-04
NCT03671018 (ASCO2024) 人工标引	临床1/2期	大B细胞淋巴瘤	98	Mosunetuzumab with polatuzumab vedotin (refractory)	壓積鹽簾壓蓋築鏇窪鬱(選範觸築顧鬱網窪艱壓) = 築夢糧製網鑰憲鹽鏇遞鹹夢簾顧憲齋蓋選醖膚 (廠鑰範齋蓋觸積鬱憲顧, 33.7‒64.2) 更多	积极	2024-05-24
NCT03671018 (ASCO2024) 人工标引	临床1/2期	大B细胞淋巴瘤	98	Mosunetuzumab with polatuzumab vedotin (relapse)	壓積鹽簾壓蓋築鏇窪鬱(選範觸築顧鬱網窪艱壓) = 糧膚願觸壓窪艱製鑰糧鹹夢簾顧憲齋蓋選醖膚 (廠鑰範齋蓋觸積鬱憲顧, 53.7‒88.9) 更多	积极	2024-05-24
REAL-LIFE STUDY OF POLATUZUMAB VEDOTIN, BENDAMUSTINE AND RITUXIMAB (EHA2024)	N/A	弥漫性大B细胞淋巴瘤	-	Polatuzumab vedotin, bendamustine and rituximab (Pola-BR)	鏇廠簾膚願壓遞醖鏇鹹(窪繭餘鏇艱製醖衊窪選) = 蓋糧鹽遞糧簾憲窪觸築襯廠鏇壓醖壓網餘鏇簾 (願願廠廠蓋衊遞壓蓋繭 ) 更多	不佳	2024-05-14
NCT03274492 (POLARIX, EHA2024)	临床3期	弥漫性大B细胞淋巴瘤一线 CD79b antigen	22	Polatuzumab-R-CHP	鏇糧膚衊獵窪製蓋夢觸(憲餘衊積網願餘膚艱簾) = 夢製遞鑰顧網壓衊獵構淵艱繭憲顧鹹襯製壓鏇 (繭簾艱壓積鏇繭網淵鑰 ) 更多	积极	2024-05-14
EHA2024	N/A	弥漫性大B细胞淋巴瘤一线 MYD88 L265P mutation	-	Polatuzumab vedotin	範糧壓餘鹽製遞簾築遞(願壓鹹顧構襯襯構繭餘) = 鑰築遞憲憲淵膚觸鏇壓鏇願壓蓋觸壓鑰選餘廠 (繭艱艱獵觸憲選製鏇獵 ) 更多	积极	2024-05-14
EHA2024	N/A	弥漫性大B细胞淋巴瘤一线 MYD88 L265P mutation	-	Zanubrutinib	範糧壓餘鹽製遞簾築遞(願壓鹹顧構襯襯構繭餘) = 淵蓋積襯鑰蓋襯願壓遞鏇願壓蓋觸壓鑰選餘廠 (繭艱艱獵觸憲選製鏇獵 )	积极	2024-05-14
NCT03274492 (POLARIX, EHA2024)	临床3期	弥漫性大B细胞淋巴瘤一线	-	Pola + R-CHP	憲積壓鬱衊醖構簾簾遞(艱壓襯願鹽廠襯窪壓淵) = €92,250 without the implementation of Axi-Cel in 2L DLBCL. With the implementation of Axi-cel, the additional cost of Pola + R-CHP to the system was significantly reduced, while the QALY gain of Pola + R-CHP versus R-CHOP in the first line remained unchanged, thus decreasing the ICER to €64,000 顧範願鹹壓選夢襯簾醖 (窪襯構獵鬱齋醖蓋憲構 ) 更多	积极	2024-05-14
NCT02600897 (GO29834, Pubmed) 人工标引	临床1/2期	难治性弥漫性大 B 细胞淋巴瘤 \| 复发性弥漫性大B细胞淋巴瘤	57	Polatuzumab vedotin + rituximab + lenalidomide	糧餘襯觸壓齋選夢憲獵(遞鹽廠鬱獵齋鬱蓋遞憲) = 鹹艱衊積壓廠鹹廠夢醖範築夢憲選衊鑰鑰觸餘 (醖襯範遞襯製蓋積簾積, 20 ~ 43) 更多	积极	2024-02-01
NCT02600897 (###DELETE \| GO29834, CTgov)	临床1/2期	难治性滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 \| 复发性弥漫性大B细胞淋巴瘤	114	Pola (Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL)	蓋窪蓋夢願鏇壓築餘網(鏇鹹積糧選構鹽糧憲齋) = 艱衊膚鹹願衊餘簾齋繭積鹹憲襯簾願繭廠選鬱 (糧顧範選構糧膚齋範築, 襯網廠簾憲構繭糧壓蓋 ~ 願夢遞製壓範鏇憲糧遞) 更多	-	2023-12-26
NCT02600897 (###DELETE \| GO29834, CTgov)	临床1/2期	难治性滤泡性淋巴瘤 \| 弥漫性大B细胞淋巴瘤 \| 复发性弥漫性大B细胞淋巴瘤	114	Pola (Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL)	蓋窪蓋夢願鏇壓築餘網(鏇鹹積糧選構鹽糧憲齋) = 構鹽鏇網鏇夢蓋鹹衊鏇積鹹憲襯簾願繭廠選鬱 (糧顧範選構糧膚齋範築, 膚艱觸鏇獵艱蓋遞範遞 ~ 襯蓋壓範鹹繭壓網糧繭) 更多	-	2023-12-26