A Study to Evaluate the Efficacy and Safety of Genotype-guided Targeted Agents in Combination With POLA-RCHP VERSUS POLA-RCHP in Patients With Previously Untreated Diffuse Large B-cell Lymphoma

The purpose of this study is to compare the efficacy and safety of genotype-guided targeted agents in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola RCHP-X) versus Pola RCHP in Chinese patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

开始日期2024-12-31

申办/合作机构-

ACTRN12623000640606 / Not yet recruiting临床2期

CLL08 - A phase 2 study of venetoclax/rituximab (VenR) re-treatment in relapsed/refractory CLL patients with disease progression following VenR as their last line of therapy

开始日期2024-09-01

申办/合作机构

Australasian Leukaemia & Lymphoma Group

NCT06341205 / Not yet recruiting临床3期IIT

Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous Nephropathy

Membranous nephropathy is an autoimmune disease affecting the kidney, and the most common cause of nephrotic syndrome in non-diabetic Caucasian adults. The course of this disease is highly variable from one individual to another, ranging from spontaneous remission to progressive chronic kidney disease.
The identification of autoantibodies - e.g., the phospholipase A2 receptor type 1 (PLA2R1) - has promoted the use of immunosuppressive drugs such as rituximab which is now a safe and effective first-line treatment for the management of membranous nephropathy. However, up to 40% of patients do not respond to a first course of rituximab treatment. In nephrotic patients, due to urinary drug loss, rituximab blood level is lower than in other autoimmune diseases treated with rituximab without proteinuria. This high urinary drug loss decreases the drug exposure, potentially explaining why rituximab regimen with low dose infusions (375 mg/m2) did not demonstrate efficacy after month-6 compared to a non-immunosuppressive antiproteinuric treatment in a previous study. In contrast, a regimen of two 1-g infusions two weeks apart was associated with a significantly greater remission rate after 6 months.
Recently, the investigators have shown that after two 1-g rituximab infusions, the rituximab blood level 3 months after the first rituximab infusion, was correlated with the likelihood of remission after 6 and 12 months of the rituximab treatment. Patients with positive rituximab blood level 3 months after treatment had a higher chance of remission at month-6 and at month-12 than patients with an undetectable rituximab level at month-3.
Nowadays, machine learning algorithms are increasingly used in medicine, especially in pharmacology, to predict the exposure to a drug, the initial dose to administer or the interval between two infusions.
The objective of this study is to use a machine learning algorithm predicting the risk of having an undetectable residual level of rituximab 3 months after treatment, in order to propose a personalized treatment management with early additional doses of rituximab for the patients at risk.

开始日期2024-09-01

申办/合作机构

Centre Hospitalier Universitaire de Nice

100 项与利妥昔单抗相关的临床结果

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100 项与利妥昔单抗相关的转化医学

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100 项与利妥昔单抗相关的专利（医药）

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26,896

项与利妥昔单抗相关的文献（医药）

2106-07-05·Oncotarget

A comparison of R-EPOCH and R-CHOP as a first-line regimen inde novoDLBCL patients with high Ki-67 expression in a single institution

Article

作者: Wang, Yu ; Sun, Peng ; Bi, Xi-Wen ; Lin, Tong-Yu ; Liu, Pan-Pan ; Xia, Yi ; Jiang, Wen-Qi ; Huang, Jia-Jia ; Li, Zhi-Ming

Diffuse large B-cell lymphoma (DLBCL) patients with high Ki-67 expression receive limited benefits from R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy. This study aims to compare the R-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and R-CHOP regimens as first-line therapy in DLBCL patients with high Ki-67 expression. Data from 44 untreated DLBCL patients with high Ki-67 expression receiving R-EPOCH therapy were matched with those from 132 untreated DLBCL patients with high Ki-67 expression receiving R-CHOP therapy based on the International Prognostic Index (IPI: age, Ann Arbor stage, performance status, LDH level, number of extranodal sites), gender, and Ki-67 expression. In the R-EPOCH group, 42/44 patients were eligible for response evaluation. A total of 35 patients (83.3%) achieved complete remission (CR); 6 patients (14.3%) achieved partial remission (PR); and one patient (2.4%) exhibited progressive disease (PD) after 2 cycles of therapy. Patients in the R-EPOCH group presented better survival outcomes than those in the R-CHOP group (3-year overall survival [OS]: 89.9% vs. 70.2%, p = 0.041; 3-year progression-free survival [PFS]: 86.6% vs. 59.7%, p = 0.024). The survival superiority of the R-EPOCH over the R-CHOP regimen persisted when considering only patients of low-to-intermediate IPI risk, but it was not observed in those of high IPI risk. Our data suggest that R-EPOCH could be superior to R-CHOP as a first-line regimen in DLBCL patients with high Ki-67 expression, especially in those of low-to-intermediate IPI risk.

2024-12-31·The Journal of dermatological treatment

The efficacy and safety of low-dose rituximab in the treatment of pemphigus vulgaris: a cohort study

Article

作者: Wang, Yiyi ; Zhan, Tongying ; Xia, Dengmei ; Xu, Xiaoxi ; Xiao, Yue ; Li, Wei ; Zhou, Xingli ; Zhou, Yuxi ; Hu, Hongxiang ; Wang, Jinqiu ; Lan, Tianjiao

BACKGROUND:

Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved.

OBJECTIVES:

To investigate the efficacy and safety of low-dose RTX (a single infusion of 500 mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX.

METHODS:

Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected.

RESULTS:

Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone.

CONCLUSIONS:

This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV.

2024-07-01·Current rheumatology reviews

Efficacy of Rituximab on Refractory Organ Involvements in Granulomatosis with Polyangiitis: A Systematic Review of Case Reports

Review

作者: Hajishah, Hamed ; Chadeganipour, Amir Shayan ; Salehi, Seyyed Amirhossein ; Amini, Mohammad Javad ; Kazemi, Danial

Introduction::

Granulomatosis with polyangiitis (GPA) is a type of Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterized by necrotizing vasculitis affecting small and medium-sized blood vessels. GPA affects various organs, with respiratory tract, vasculitis and glomerulonephritis being the most common triad. Remission induction and maintenance therapy for GPA traditionally involves corticosteroids and cyclophosphamide. However, treatment with rituximab, a monoclonal antibody that depletes B-cells involved in autoimmune disease, has been successful in inducing remission in several studies. The purpose of this systematic review was to investigate the efficacy of rituximab in treating various clinical manifestations of GPA.

Methods::

In adherence to PRISMA guidelines for systematic reviews and meta-analyses, we carried out a comprehensive review to investigate the effectiveness of rituximab on particular organ involvement in GPA. We searched three databases (PubMed, Scopus, and Embase) up until November 6, 2022, for case reports on the topic. To ensure all relevant studies were included, we manually screened the first 50 pages of Google Scholar's search results.

Results::

The review identified a total of 64 case reports and a case series of 113 cases, highlighting the effectiveness of rituximab in treating refractory organ involvement in GPA. The review also analyzed the effectiveness of rituximab in treating ocular, CNS, cardiac, pulmonary, cutaneous, gastrointestinal, renal, and other organ involvements in GPA.

Conclusions::

Our results indicated that rituximab can be a promising therapy for treating specific clinical manifestations of several organ involvements. However, more research is needed to determine the long-term efficacy of rituximab in treating GPA.

1,851

项与利妥昔单抗相关的新闻（医药）

2024-06-21

·药智网

股价暴涨480%！美国Biotech闷声发财

A股一片绿油油，在大洋彼岸，这家Biotech正闷声发财。近日，美国公司Mustang Bio宣布其CD20 CAR-T疗法MB-106针对华氏巨球蛋白血症患者取得积极临床数据，当天消息一出，公司股价暴涨近480%。股价暴涨背后，又一款大药将引爆市场。 01 无法治愈的痛华氏巨球蛋白血症（WM）是一类惰性B细胞非霍奇金淋巴瘤。根据美国癌症协会，WM多发于男性白人，美国每年发病率为万分之0.03。尽管WM在非霍奇金淋巴瘤中的占比较低，但目前却无法治愈，对于没有症状的WM患者，治疗无法带来益处，存在巨大未被满足的临床需求。对于有症状的WM患者，可采用CD20单抗、BTK抑制剂、蛋白酶体抑制剂、BCL-2抑制剂等治疗，但这些现有治疗方案均有不足。 MB-106是一款靶向CD20的自体CAR-T细胞疗法，已被优化为第三代全人源抗体。根据Mustang Bio披露的I/II期临床试验数据显示，接受MB-106治疗的华氏巨球蛋白血症患者的总缓解率（ORR）高达90%，包括3例患者达到完全缓解，其中1位患者持久完全缓解达31个月。值得一提的是，参与这项研究的全部10名患者，此前都接受过BTK抑制剂治疗，但用药期间病情仍然持续进展。安全性方面，9例患者发生了细胞因子释放综合征（CRS），其中5例为1级，4例为2级，1例经历了1级免疫效应细胞相关神经毒性综合征（ICANS）。尽管剂量增加，也未观察到3级或4级CRS或2、3或4级ICANS。换句话说，这项临床数据十分亮眼，展现出了优异的有效性和安全性。 Mustang Bio的研发管线图片来源：Mustang Bio公司官网 MB-106不仅展现了亮眼的临床数据，更以其创新性和填补市场空白的潜力，吸引了投资者的目光，从而推动股价暴涨。 02 全球0款当前，全球尚未有针对CD20靶点的CAR-T疗法获批上市，同时FDA也尚未批准用于治疗华氏巨球蛋白血症（WM）的CAR-T疗法，市场处于空白状态。如果MB-106能成功获得批准，将可享有较高的市场定价权和市场独占性。再加上，目前全球已获批上市的CAR-T疗法，主要集中在CD19或BCMA靶点，出现了同质化的现象，使得资本市场对于新靶点的CAR-T疗法抱有更高的预期。 Mustang Bio股价得以暴涨的关键因素，就在于市场预见到了CD20 CAR-T疗法巨大的发展潜力和商业价值。 MB-106不仅在针对WM患者的临床试验中展现出了亮眼临床数据，而且还在开发其他适应症，包括用于治疗复发或难治性B细胞非霍奇金淋巴瘤（B-NHL）和慢性淋巴细胞白血病（CLL）患者。图片来源：中信建投证券 CLL和WM适应症都属于成熟B细胞肿瘤，其中CLL患者人数更多，在非霍奇金淋巴瘤中占有较大比重，是血液肿瘤领域的“兵家必争之地”。许多“重磅炸弹”都拿下了CLL适应症，包括罗氏的年销售额曾超过70亿美元的“CD20单抗之王”利妥昔单抗，以及BTK抑制剂，如强生/艾伯维的伊布替尼、百济神州的泽布替尼。这些药物的广泛应用和卓越市场表现，凸显了CD20靶点在治疗B细胞相关疾病中的关键作用。作为靶向CD20的CAR-T疗法，MB-106已在临床研究中展现出了令人瞩目的疗效数据。基于其卓越的临床表现和不断扩展的适应症范围，我们可以合理推测MB-106具备成为大药的潜力。值得一提的是，已完成6轮融资的宜明细胞，是Mustang Bio的“卖水人”。去年5年，宜明细胞收购了Mustang Bio位于马萨诸塞州伍斯特市顶级的GMP细胞与基因治疗（CGT）生产基地相关资产，并负责Mustang Bio的一系列在研药物（包括正在进行的多中心I/II期试验的MB-106以及其它管线）的CDMO及商业化生产等事宜。 03 巨头青睐事实上，早在2023年5月，CD20 CAR-T疗法就获得了全球制药巨头的青睐。彼时，强生旗下杨森制药与西比曼生物达成一项全球独家合作，共同开发和商业化下一代新型CAR-T细胞治疗产品C-CAR039（靶向CD19/CD20）和C-CAR066（靶向CD20）。根据协议，杨森制药将获得中国以外地区C-CAR039和C-CAR066独家开发权，以及中国地区开发的优先选择权；西比曼生物将获得2.45亿美元的首付款、后续多笔里程碑付款以及销售分成。西比曼生物曾于2014年在美股上市，是首个在纳斯达克上市的中国细胞治疗生物科技公司，之后于2021年完成私有化并退市。值得一提的是，这已经不是强生第一次布局CAR-T疗法。早在2017年，强生就与传奇生物达成全球独家许可合作，开发和商业化靶向BCMA的CAR-T疗法Carvykti（西达基奥仑赛，Cilta-cel），并收获了不错的业绩。 2023年，Carvykti实现销售额达5亿美元，今年一季度再以118%的同比增速实现1.57亿美元，市场预计其今年有望突破10亿美元成为“重磅炸弹”。图片来源：国联证券斥巨资拿下，强生引进的这两款新型CAR-T疗法（C-CAR039、C-CAR066），到底能不能打？ C-CAR039是新型CD19/CD20双靶点CAR-T疗法，正在美国开展治疗复发或难治性（r/r）B细胞非霍奇金淋巴瘤（B-NHL）患者的Ⅰb期研究。根据西比曼生物在2023年ASH年会公布C-CAR039的研究数据显示：在47例可评价的r/r NHL患者中，总体缓解率（ORR）为91.5%，完全缓解率（CR）为85.1%，中位随访时间为30个月。 C-CAR066是靶向CD20的第二代CAR-T疗法，目前正在美国开展针对r/r大B细胞淋巴瘤（LBCL）患者（包括先前CD19 CAR-T治疗失败的患者）的Ⅰb期研究。根据西比曼生物在2023年ASH年会公布C-CAR066的研究数据显示：在既往CD19 CAR-T治疗失败的LBCL患者中，ORR为92.9%，CR率为57.1%，中位随访时间27.7个月，中位PFS和DOR分别为9.4个月和8.3个月。从全球市场看，据不完全统计，目前进入临床阶段的CD20 CAR-T疗法已超过10款，布局者多为国内药企，包括隆耀生物的LY007、Adicet Bio的ADI-001、Kite的两款CD19/CD20双靶点CAR-T疗法（KITE-363和KITE-753）等，适应症均为血液肿瘤，不过研发进度相差不大，国内药企有望脱颖而出。 04 结语创新是区别领导者和追随者的唯一标准。随着Mustang Bio的MB-106在治疗难以根治的华氏巨球蛋白血症上展现出潜力，这款疗法有望填补当前市场的治疗空白。参考资料 1.各家公司的财报、公告、官微 2.《90%患者达成缓解！CAR-T疗法最新积极临床结果公布》，药明康德，2024-06-19 3.《20220929-诺诚健华-9969.HK-主打小分子药物的创新药企，拥有潜在同类最佳的BTK抑制剂》，安捷证券 4.中信建投证券、国联证券声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 德清君转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

细胞疗法临床1期免疫疗法ASH会议上市批准

2024-06-20

·药精通Bio

创新药一哥被围剿

深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，展位咨询&免费入场券：联系电话181 1603 6798，扫码立即获取免费入场券：血液瘤后浪催化密集来袭。众所周知，“创新药一哥”百济神州国际化的安身立命之本主要在血液瘤领域，仅泽布替尼收入占2023年公司全部产品收入近60%，而后续临近商业化最具想象力的部分也在于“Bcl2、BTK Protac”构建的血液瘤适应症覆盖版图。百济神州显然知道在这些热门靶点迭代内卷激化的背景下，兵贵神速是最能够突围而出的路线之一，快速对Bcl2、BTK Protac两个领域开启了临床大三期的探索，其中还针对“BGB-11417+泽布替尼”的组合设计了头对头“维奈克拉+奥妥珠单抗”的大三期。近期，阿斯利康的Calquence（阿卡替尼）和Nurix Therapeutics的NX-5948释放的惊艳临床数据，无疑会让百济神州的“压力倍增”。 01 阿斯利康在努力，礼来虎视眈眈 BTK抑制剂市场如今三分天下，伊布替尼市场份额逐渐被阿卡替尼、泽布替尼蚕食。2023年，泽布替尼的放量趋势很快，未来隐隐有坐大的潜力；2023Q3-2023Q4，阿卡替尼季度收入实现6.56亿美元、6.75亿美元，而泽布替尼分别实现3.58亿美元、4.13亿美元，一边阿卡替尼环比增速放缓，一边泽布替尼环比快速增长，让投资者看到了泽布替尼成为BTK全球销售龙头的潜力。阿卡替尼正在用力扩大治疗范围，以求率先覆盖泽布替尼目前触及不到的适应症领域。 6月16日，在2024年EHA大会上，阿斯利康公布ECHO三期试验的积极结果显示：阿卡替尼联合苯达莫司汀和利妥昔单抗一线治疗套细胞淋巴瘤（MCL）展现良好总生存期（OS）趋势。对比标准化学免疫疗法（苯达莫司汀加利妥昔单抗），阿卡替尼联合治疗方案展现出几大优势： 1）阿卡替尼联合治疗方案将疾病进展或死亡的风险降低了27%； 2）阿卡替尼联合治疗的患者的中位PFS为66.4个月（n=299），而接受标准护理化学免疫治疗的患者的中位PFS为49.6个月（n=299）； 3）OS的次要终点显示出阿卡替尼联合疗法的有利趋势，进一步支持了该联合疗法的临床获益。不过OS数据尚未成熟，试验将继续评估OS作为关键的次要终点。这意味着，BTK抑制剂的市场竞争将日益激烈，泽布替尼、阿卡替尼要达到伊布替尼的高度，必须加快向更多早线血液瘤患者进发，一线治疗也将成为日后两者竞争最激烈的领域。 BTK抑制剂的后浪，礼来的Jaypirca也正在虎视眈眈。目前，Jaypirca在美国已经获批了套细胞淋巴瘤、慢性淋巴细胞白血病和小淋巴细胞性淋巴瘤3个适应症（两次加速批准），同时礼来预计2030年Jaypirca将在慢淋市场占据60%市场份额，对应30亿美元的年销售额。当然，Jaypirca的疗效足够惊艳。据最新披露的BRUIN 1/2期研究数据显示，接受Jaypirca治疗的患者（既往接受过BTK抑制剂治疗、治疗基线中位值为四线）总缓解率（ORR）为81.6%，中位无进展生存期（mPFS）为19.4个月。在接受过共价BTK抑制剂和BCL-2抑制剂治疗的患者中（治疗基线中位值为五线），Jaypirca治疗组的ORR为79.7%，中位PFS为15.9个月。另外，礼来为了证明Jaypirca是BTK抑制剂中的“Best in class”，在BRUIN MCL-321的临床中选择以一敌三，头对头伊布替尼、泽布替尼、阿卡替尼。 02 Nurix的proatac分子疗效惊艳蛋白降解技术被市场认为是“小分子的未来”，嗅觉敏锐的研发厂商迅速投入BTK protac这一赛道，百济神州在去年公布了BGB-16673的初步数据，另一海外厂商Nurix Therapeutics也在最近公布了旗下NX-5948的优异数据。 6月16日，Nurix最新公布NX-5948的1a/b期临床数据显示，在基线为四线的CLL患者中，NX-5948均能使患者获得快速、深度的缓解，客观缓解率（ORR）高达69.2%。值得注意的是，临床中的31例患者大量接受过共价BTK抑制剂（96.8%）、BCL-2抑制剂（90.3%）等方式的治疗，并且大量患者在过去出现与BTK抑制剂耐药相关的突变，这凸显出NX-5948的疗效强度；安全性方面，最常见的治疗紧急不良事件包括紫癜/挫伤、血小板减少症和中性粒细胞减少症等。其中，最惊艳的莫过于Nurix公司展示的两个病例： 1）一名既往接受过11线治疗包括所有可用的BTK抑制剂（甚至包括礼来的Jaypirca）的患者，在每天使用200mg NX-5948 治疗后，患者在第8周时获得了反应，随着时间的推移而加深，并持续了超过6个月的随访； 2）一名接受过三种既往治疗（包括BTK抑制剂）且带有脑转移的患者，每天用100 mg和300 mg的NX-5948治疗后，在36周时表现出接近完全缓解标准的加深反应，并在24周内消除脑脊液中的恶性细胞。对于BGB-16673的早期数据，过去百济神州只披露了复发难治B细胞恶性肿瘤和慢淋少量数据，在2023年11月公布的慢淋一期临床数据中，其患者总体基线与NX-5948临床相近（中位年龄：70 vs 69、基线数均为4、TP53突变：50% vs 46.7%、接受过Bcl-2治疗：87% vs 90.3%、接受过共价BTK治疗的：95% vs 96.8%），取得的ORR约为67%（NX-5948最后ORR可评估患者为26人，BGB-16673取得上述数据可评估患者为21人）。小样本数据虽然无法说明什么，但至少BGB-16673目前拥有NX-5948这样的一个“势均力敌”的对手，分水岭可能在2/3期数据兑现时就能拉开。 03 Bcl-2竞争也不轻松 Bcl-2抑制剂的研发，可能是相对BTK抑制剂和降解剂竞争较为缓和的，但依然不轻松。 Bcl-2抑制剂的全球第二名，注定要在百济神州和亚盛医药两者之中决出。从时间维度上审视，亚盛医药APG-2575的注册性三期临床在2023年8月被FDA批准，百济神州则是在2023年10月初启动了BGB-11417联用泽布替尼的头对头大三期临床，两者的差距并不明显。不过从两者资金实力和过往的海外临床能力&执行力看，似乎百济神州综合实力更胜一筹。从临床数据维度审视（非头对头、供参考），APG-2575和BGB-11417在不同层面各有胜负，单药前者在爬坡剂量速度和安全性上更有潜力，后者则是在与泽布替尼的联用疗法组合上疗效和安全性更有潜力，最终还是要在三期数据兑现和执行速度上决一胜负，毕竟第二名和第三名，区别巨大。但显而易见的是，两者都解决了艾伯维的Bcl-2抑制剂维奈克拉存在的一些问题，均具备me-better的潜力。（分析详见：下一个国产药出海重磅炸弹）另外在后浪追赶者层面，目前有不少的国产厂商正在奋起直追，包括复创医药的FCN-338、正大天晴的TQB3909、麓鹏制药LP-118和诺诚健华的ICP-248等。至于在迭代疗法领域，目前主要的策略为双靶向“Bcl-2+X”，如Bcl-2/Bcl-xl以解决Bcl-2突变对第一代抑制剂维奈托克的耐药。更新的迭代药物研发方式，便是研发Bcl-xL和Bcl-2双降解剂，以实现对目标细胞的的持续降解。结语：继泽布替尼之后，百济神州能不能凭借高效的临床执行力在Bcl-2和BTK prtac杀出一条血路，将决定公司能否“拿下Pharam进阶敲门砖”这一重大里程碑，我们拭目以待。免责声明：本文信息来源于网络，本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 END 深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话18116036798上下滑动查看议程戳“阅读原文”立即报名多肽药物论坛吧!

临床3期免疫疗法蛋白降解靶向嵌合体

2024-06-20

·BioSpace

NIH Finds Non-Chemo Drug Combo Induces Lasting Remission in DLBCL Patients

Pictured: The National Institutes of Health's main building in Maryland/iStock, Grandbrothers Researchers from the National Institutes of Health have identified a novel, non-chemotherapy combination regimen for treating relapsed diffuse large B-cell lymphoma, reporting full remission for some patients no longer responding to standard treatments. Detailing their findings Wednesday in The New England Journal of Medicine, the NIH scientists combined five common anti-cancer agents—AbbVie and Genentech’s Vencelxta (venetoclax), Johnson & Johnson’s Imbruvica (ibrutinib), Genentech’s Gazyva (obinutuzumab), Bristol Myers Squibb’s Revlimid (lenalidomide) and the corticosteroid prednisone. The treatment combo, dubbed ViPOR, was tested in a Phase Ib/II study that included 50 patients with diffuse large B-cell lymphoma (DLBCL). Results showed that the investigational regimen “substantially” shrank tumors in 28 of 48 evaluable patients, according to the NIH. This corresponded to a 54% objective response rate. Overall, 18 patients saw their tumors completely disappear, resulting in a 38% complete response rate for ViPOR. At the end of treatment, circulating tumor DNA was undetectable in 33% of patients. After two years of follow-up, 34% of treated patients showed no signs of the disease while 36% remained alive. In terms of safety, the Phase Ib portion of the study detected a single dose-limiting case of grade 3 intracranial hemorrhage. In the Phase II portion, adverse events of note included grade 3 or 4 neutropenia, thrombocytopenia, anemia and febrile neutropenia. “DLBCL is one of the most genetically heterogeneous forms of cancer, and as a result we don't yet have the ability to identify exactly which combination of drugs would be most effective for any given patient,” Christopher Melani, from the National Cancer Institute’s Center for Cancer Research, said in a statement. Melani co-led the study. “By putting five drugs together, we believe that there will be some drug combination—either two, three, or more drugs—that will be particularly effective against the patient’s tumor,” Melani said. The NIH researchers are working on a larger Phase II study, which they plan to conduct in multiple centers. The mid-stage trial will assess the activity of ViPOR in various genetic subtypes of DLBCL. Accounting for around 25% to 30% of all non-Hodgkin lymphomas, DLBLC is the most common type of lymphoma, according to the NIH. It is typically characterized as the enlargement of lymph nodes or the rapid growth of a mass in a nodal or extranodal site. DLBCL is often aggressive, though it responds reasonably well to a regimen called R-CHOP, which consists of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Several pharma players are working on potentially better therapies for DLBCL to improve safety and efficacy, as well as provide patients more options in case of disease progression or treatment intolerance. Pfizer is advancing its antibody-drug conjugate Adcetris (brentuximab vedotin) for DLBCL and in March 2024 reported that it significantly improved survival in patients enrolled in the Phase III ECHELON-3 study. Roche is also targeting DLBCL with its bispecific T-cell engager Columvi (glofitamab) boosting survival in the Phase III STARGLO trial, according to an April 2024 readout. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床结果临床2期抗体药物偶联物临床3期临床1期

100 项与利妥昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02994	利妥昔单抗	L01XC02	DB00073

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
心脏移植排斥反应	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
肝移植排斥反应	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
肺移植排斥反应	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
胰腺移植排斥反应	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
肾移植排斥反应	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
小肠移植排斥	日本	Zenyaku Kogyo Co., Ltd.	2023-12-22
视神经脊髓炎	日本	Zenyaku Kogyo Co., Ltd.	2022-06-20
巴西天疱疮	日本	Zenyaku Kogyo Co., Ltd.	2021-12-24
家族性寻常型天疱疮	日本	Zenyaku Kogyo Co., Ltd.	2021-12-24
获得性血栓性血小板减少性紫癜	日本	Zenyaku Kogyo Co., Ltd.	2020-02-21
CD20阳性B细胞慢性淋巴细胞白血病	日本	Zenyaku Kogyo Co., Ltd.	2019-03-26
淋巴细胞白血病	日本	Genentech, Inc.	2019-03-26
淋巴细胞白血病	日本	IDEC Pharmaceuticals Corp.	2019-03-26
慢性特发性血小板减少性紫癜	日本	Zenyaku Kogyo Co., Ltd.	2017-06-26
血小板减少性紫癜	日本	Genentech, Inc.	2017-06-26
血小板减少性紫癜	日本	IDEC Pharmaceuticals Corp.	2017-06-26
肾病综合征	日本	Zenyaku Kogyo Co., Ltd.	2014-08-29
肾病综合征	日本	IDEC Pharmaceuticals Corp.	2014-08-29
肾病综合征	日本	Genentech, Inc.	2014-08-29
血管炎	中国台湾	Roche Holding AG	2012-12-31

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
肿瘤	申请上市	加拿大	Dr. Reddy's Laboratories SA	-
难治性B细胞淋巴瘤	临床3期	美国	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	中国	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	日本	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	阿根廷	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	巴西	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	加拿大	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	以色列	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	墨西哥	Hoffmann-La Roche, Inc.	2022-04-25
难治性B细胞淋巴瘤	临床3期	新西兰	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


NCT00268853 (CTgov)	临床2期	弥漫性大B细胞淋巴瘤	124	rituximab+Cyclophosphamide+Prednisone+pixantrone+CPOP-R+vincristine (CPOP-R)	衊糧鹽廠憲繭糧窪憲鹽(獵衊網簾積鏇衊蓋製膚) = 顧壓醖艱壓齋網鹹餘願鑰壓積鏇蓋繭簾壓壓築 (顧獵齋製廠蓋齋積衊構, 餘遞餘襯鑰蓋鑰獵遞廠 ~ 鬱遞網願鏇鹹範製壓築) 更多	-	2024-05-30
				rituximab+Cyclophosphamide+Prednisone+doxorubicin+vincristine+CHOP-R (CHOP-R)	衊糧鹽廠憲繭糧窪憲鹽(獵衊網簾積鏇衊蓋製膚) = 選糧製製繭選壓築繭襯鑰壓積鏇蓋繭簾壓壓築 (顧獵齋製廠蓋齋積衊構, 壓鑰艱膚糧鑰憲淵遞淵 ~ 範淵醖顧蓋糧鹽鑰鏇淵) 更多
NCT02073097 (CTgov)	临床1/2期	弥漫性大B细胞淋巴瘤	48	Pegfilgrastim+Acyclovir+carfilzomib+cyclophosphamide+Prednisone+doxorubicin hydrochloride+Vincristine sulfate+Rituximab	衊鬱構簾鬱積餘蓋廠醖(壓選選顧網鹹顧醖壓繭) = 窪鬱糧糧艱憲觸夢衊廠顧鏇製襯糧壓艱願築廠 (網鑰襯衊齋齋艱鹹願網, 願齋網遞網鹹憲齋遞鹽 ~ 顧夢膚餘鹹淵鹽淵蓋廠) 更多	-	2024-05-29
NCT04663347 (EPCORE NHL-2, ASCO2024) 人工标引	临床1/2期	滤泡性淋巴瘤一线 \| 维持 CD20 Positive	41	Epcoritamab + rituximab + lenalidomide (arms 6)	鑰願鏇製製糧範淵夢築(構獵鹹蓋齋膚選獵鹹鏇) = 壓積選鏇願觸顧餘窪範廠觸鏇壓築範壓鹽廠窪 (壓蓋鏇鏇蓋淵積製獵膚 ) 更多	积极	2024-05-24
				Epcoritamab maintenance (arms 7)	顧齋蓋廠齋構膚繭鹽選(憲鹹鹽憲簾鏇觸觸醖鑰) = 醖艱夢廠糧積鑰壓醖繭網積願齋餘衊蓋鹽襯艱 (鏇餘繭憲製鑰蓋衊壓遞 ) 更多
ASCO2024	N/A	免疫性血小板减少症二线	60	Rituximab	顧餘齋廠窪範觸膚壓襯(遞衊遞膚繭製襯範觸窪) = 遞憲繭壓艱襯網蓋網簾選鹽願鹽衊壓壓齋範鏇 (遞窪觸築衊醖鑰範襯鏇 )	积极	2024-05-24
ASCO2024	N/A	套细胞淋巴瘤维持	90	Rituximab maintenance	艱鏇構壓壓襯衊積窪餘(淵糧艱膚鑰範蓋醖顧襯) = 鏇觸淵夢艱獵願製鹹觸鏇積夢鹽獵製簾網築構 (憲顧鹹襯膚憲齋蓋鹽獵 ) 更多	积极	2024-05-24
				rituximab	艱鏇構壓壓襯衊積窪餘(淵糧艱膚鑰範蓋醖顧襯) = 鬱簾鏇構壓鏇蓋築鏇鏇鏇積夢鹽獵製簾網築構 (憲顧鹹襯膚憲齋蓋鹽獵 ) 更多
MAINTAIN (ASCO2024)	N/A	套细胞淋巴瘤维持	796	Rituximab maintenance	艱鏇廠鏇衊簾獵淵鏇鬱(夢餘廠顧鬱糧觸範夢淵) = 簾憲艱築糧餘餘餘鬱獵鬱鹽窪餘積範窪鑰網窪 (蓋憲艱衊艱繭製襯醖淵 ) 更多	积极	2024-05-24
				No rituximab maintenance	艱鏇廠鏇衊簾獵淵鏇鬱(夢餘廠顧鬱糧觸範夢淵) = 鬱構艱構夢觸簾繭願製鬱鹽窪餘積範窪鑰網窪 (蓋憲艱衊艱繭製襯醖淵 ) 更多
ASCO2024	N/A	原发性中枢神经系统淋巴瘤	-	Orelabrutinib	蓋獵網簾願餘選壓範顧(選觸築鹽窪衊糧鑰繭夢) = Only 1 (10%) pts experienced ≥grade 3 AEs—acute kidney injury 積艱壓廠獵壓壓壓壓鹹 (膚夢憲網鹽鏇製觸醖夢 ) 更多	-	2024-05-24
				Rituximab
NCT02460276 (PHILEMON, EHA2024) 人工标引	临床2期	复发性套细胞淋巴瘤 TP53 mutation	50	Ibrutinib+Lenalidomide,+Rituximab	構簾窪選築選醖鏇醖艱(網夢遞壓鹹窪蓋積憲選) = 鹽餘築觸顧鹹衊齋夢築鹹簾簾構網鬱憲製襯蓋 (鬱糧廠齋簾窪膚觸網廠, 21.1 ~ NE) 更多	积极	2024-05-14
NCT04624958 (CHESS, EHA2024) 人工标引	临床2期	套细胞淋巴瘤一线	42	Zanubrutinib + rituximab (ZR) +SHORT COURSE R-DHAOX	觸齋鏇餘積鹹糧醖膚衊(憲鏇廠網製獵簾簾襯築) = 糧夢齋顧窪鹽選廠壓齋鏇鹽鹹選壓襯繭選構網 (簾選餘壓構糧獵顧夢餘 ) 更多	积极	2024-05-14
EHA2024	N/A	慢性淋巴细胞白血病 del(17p) \| TP53 mutation \| unmutated IGHV status	-	Venetoclax + Obinutuzumab	鏇製蓋壓糧觸鏇構窪遞(壓憲築窪餘窪簾製鹹膚) = 憲鑰積衊壓積願鹹獵鬱鹹觸鏇繭衊簾鹽壓蓋齋 (壓願齋網蓋餘觸窪窪夢 ) 更多	积极	2024-05-14
				Venetoclax + Rituximab	鏇製蓋壓糧觸鏇構窪遞(壓憲築窪餘窪簾製鹹膚) = 鹹廠願窪鹹齋構鬱壓繭鹹觸鏇繭衊簾鹽壓蓋齋 (壓願齋網蓋餘觸窪窪夢 ) 更多