预约演示

更新于：2025-09-30

Bevacizumab

贝伐珠单抗

更新于：2025-09-30

概要

基本信息

药物类型

单克隆抗体

别名

Bevacizumab(Genetical Recombination)、rhuMAb-VEGF、贝伐单抗

+ [17]

靶点

VEGF-A

作用方式

抑制剂

作用机制

VEGF-A抑制剂(血管内皮生长因子A抑制剂)、血管生成抑制剂

治疗领域

肿瘤神经系统疾病消化系统疾病+ [11]

在研适应症

不可切除的肝细胞癌肝细胞癌复发性胶质母细胞瘤+ [219]

非在研适应症

异戊酸血症急性嗜碱性粒细胞白血病急性嗜酸细胞白血病+ [281]

原研机构

Genentech, Inc.

在研机构

Hoffmann-La Roche, Inc.

National Cancer InstituteMerck Sharp & Dohme LLC

+ [26]

非在研机构

SanofiNSABP Foundation, Inc.

Mayo Clinic

+ [53]

权益机构

Roche Korea Co., Ltd.

Immune-Onc Therapeutics, Inc.

Roche Holding AG

+ [5]

最高研发阶段批准上市

首次获批日期

美国 (2004-02-26),

结肠癌直肠癌

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、加速批准 (美国)、孤儿药 (美国)

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结构/序列

Sequence Code 41632H

来源: *****

Sequence Code 41637L

来源: *****

关联

3,409

项与贝伐珠单抗相关的临床试验

NCT06696768

/ Recruiting临床1期IIT

Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer

This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.

开始日期2026-01-23

申办/合作机构

National Cancer Institute

NCT07198074

/ Not yet recruiting临床3期IIT

A Randomized Phase II/III Trial of Carboplatin, Paclitaxel, Pembrolizumab Versus Carboplatin, Paclitaxel, Bevacizumab Versus Carboplatin, Paclitaxel, Pembrolizumab, Bevacizumab in the Treatment of pMMR, TP53 Mutated Advanced or Recurrent Endometrial Cancer

This phase III trial compares the effect of bevacizumab in combination with carboplatin, paclitaxel and pembrolizumab to the usual treatments of carboplatin and paclitaxel with or without pembrolizumab in treating patients with stage III, IVA or IVB mismatch repair protein proficient (pMMR) and TP53 mutated endometrial cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has come back after a period of improvement (recurrent). Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adding bevacizumab to the combination of carboplatin, paclitaxel and pembrolizumab may be more effective than the usual treatment combinations of carboplatin and paclitaxel with or without pembrolizumab in treating patients with advanced or recurrent pMMR and TP53 mutated endometrial cancer.

开始日期2025-12-15

申办/合作机构

National Cancer Institute

NCT06264531

/ Not yet recruiting临床2/3期IIT

Evaluation of the Efficacy and Safety of Anti-angiogenic Therapy With Intravenous Bevacizumab in Patients With Symptomatic Cerebral Arteriovenous Malformations

Brain arteriovenous malformations (AVMs) are responsible for hemorrhagic strokes, particularly in children and young adults. They can also be responsible for chronic neurological disorders: motor or sensory deficits, disturbances of higher functions, epilepsy or disabling headaches. The management of brain AVMs is complex and requires a multidisciplinary approach in an expert center. Available therapies include endovascular embolization, neurosurgical resection and/or radiosurgery. These procedures carry a risk of neurological complications, and are reserved for small AVMs located at a distance from highly functional cerebral structures. To date, no drug therapy is recommended if interventional treatment is not possible.
Several studies on resected brain AVM tissue have demonstrated that these malformations are the site of significant evolutionary inflammatory and neo-angiogenesis processes. Other studies have specifically shown that VEGF (vascular endothelial growth factor) levels are increased in AVMs. More recently, a pre-clinical study showed that anti-angiogenic treatment with Bevacizumab reduced vascular proliferation within AVMs in mice. Finally, a Phase II clinical trial in patients with Rendu-Osler disease (a genetic vascular disorder characterized by recurrent epistaxis, cutaneous telangiectasia and the presence of visceral AVMs) showed a clinical benefit of IV Bevacizumab on the symptomatology of these vascular malformations, with a reduction in the risk of hemorrhage and the extent of hepatic arteriovenous shunts. A randomized Phase III trial is currently underway (NCT03227263) to assess the efficacy of IV Bevacizumab in Rendu-Osler disease.
The aim of our study is to assess the efficacy of IV Bevacizumab on the disabling symptoms associated with symptomatic brain AVMs.

开始日期2025-12-01

申办/合作机构

Fondation Ophtalmologique Adolphe de Rothschild

100 项与贝伐珠单抗相关的临床结果

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100 项与贝伐珠单抗相关的转化医学

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100 项与贝伐珠单抗相关的专利（医药）

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22,455

项与贝伐珠单抗相关的文献（医药）

2026-04-01·DEN open

Long‐term results of palliative placement of very low‐axial force self‐expandable metallic stents for malignant colorectal obstruction

Article

作者: Moroi, Rintaro ; Kuwai, Toshio ; Yoshida, Shuntaro ; Enomoto, Toshiyuki ; Tomita, Masafumi ; Kyo, Rika ; Shiratori, Toshiyasu ; Saida, Yoshihisa ; Matsuzawa, Takeaki ; Isayama, Hiroyuki ; Sumida, Yorinobu ; Yamada, Tomonori ; Sasaki, Takashi

Abstract:

Objectives:

Stent placement is a standard option for palliative decompression in patients with malignant colorectal obstruction. Long‐term stent placement is associated with perforation, migration, and stent occlusion. Perforation is associated with life expectancy. Several studies have shown that stents with a high axial force (AF), which is defined as the force required to maintain the stent straight after it has bent, are associated with a higher perforation rate. Therefore, we evaluated the long‐term outcomes of using a very low AF stent (Niti‐S Enteral Colonic Uncovered stent D‐type) for palliative purposes.

Methods:

Eighty‐one consecutive patients with malignant colorectal obstruction in 33 medical institutions were evaluated. A stent with very low AF was placed using an endoscope system. We evaluated the adverse events (including perforation, migration, and stent occlusion), 1‐year survival rate, and cumulative patency rate. Univariate analysis was conducted using Fisher's exact test. The overall survival and cumulative patency rates were assessed using the Kaplan–Meier method.

Results:

The 1‐year cumulative survival rate was 37.8% after stent placement. The 3‐month, 6‐month, and 1‐year cumulative patency rates after stenting were 93.6%, 84.2%, and 75.8%, respectively. The major adverse events included stent migration (6.2%), stent occlusion (9.9%), and perforation (2.5%). Chemotherapy was administered in 26 cases (32.1%) after stenting, and bevacizumab was administered in five cases. However, no cases of perforation occurred following bevacizumab administration.

Conclusions:

Our results suggest that very low AF stents are safe and effective. Therefore, they may be a suitable option for applications, such as palliation. (UMIN 000011304)

2026-01-01·DRUG RESISTANCE UPDATES

Gamma-synuclein drives bevacizumab resistance in colorectal cancer via VEGFR2 activation and angiogenesis

Article

作者: Shou, Chengchao ; Meng, Lin ; Wang, Lixin ; Liu, Caiyun ; Qu, Like ; Dong, Bin ; Zhao, Chuanke

BACKGROUND:

Resistance to Bevacizumab (Bev) remains a major obstacle in colorectal cancer (CRC) treatment. Gamma-synuclein (SNCG), overexpressed in tumor vasculature and cancer cells, is investigated here for its role in Bev resistance and therapeutic potential.

METHODS:

Using isogenic CRC models with SNCG overexpression or knockout, we assessed SNCG's impact on Bev response in vitro and in vivo. The therapeutic efficacy of combining Bev with an anti-SNCG monoclonal antibody (42#) was evaluated in Bev-resistant models. Mechanistic studies, including ELISA, Western blot, surface plasmon resonance (SPR), and molecular docking, explored interactions between SNCG, VEGF, and VEGFR2.

RESULTS:

SNCG overexpression reduced Bev sensitivity by impairing the inhibition of migration, invasion, and spheroid formation, whereas SNCG knockout enhanced therapeutic response. Molecular docking revealed that SNCG binds VEGFR2 at an allosteric site, forming a stable ternary complex (SNCG-VEGF-VEGFR2) with enhanced hydrogen bonding, which sustained VEGFR2 phosphorylation and angiogenesis. In vivo, SNCG-overexpressing tumors showed reduced responsiveness to Bev (42.8 % inhibition vs. 64.3 % in controls, p < 0.05), while SNCG-deficient tumors exhibited a 3.2-fold increase in sensitivity. Combining Bev with 42# synergistically suppressed tumor growth (0.70 ± 0.36 g vs. 1.55 ± 0.41 g, p = 0.003), reduced metastatic burden (0.29 ± 0.23 g vs. 0.97 ± 0.42 g, p = 0.006), and extended median survival (86.8 vs. 69.8 days, p = 0.033) in Bev-resistant models.

CONCLUSIONS:

SNCG drives Bev resistance in CRC by forming a ternary complex with VEGF and VEGFR2, enhancing VEGFR2 signaling and angiogenesis. Dual targeting of VEGF and SNCG represents a promising therapeutic strategy to overcome Bev resistance, with the potential to improve outcomes in CRC patients.

2025-12-31·JOURNAL OF MEDICAL ECONOMICS

Cost-effectiveness analysis of regorafenib dose optimization for refractory metastatic colorectal cancer

Article

作者: Appukkuttan, Sreevalsa ; Cho, Sang Kyu ; Barzi, Afsaneh ; Grossman, Jamie ; Lee, Woojung ; Babajanyan, Svetlana ; Hocum, Brian ; Yang, Min ; Marian, Marisca ; Bekaii-Saab, Tanios

BACKGROUND:

New regimens have emerged as third-line or later therapies for metastatic colorectal cancer (mCRC), including regorafenib dose optimization (ReDO), trifluridine/tipiracil and bevacizumab (TAS-BEV) combination therapy, and fruquintinib. We evaluated relative cost-effectiveness of these therapies in patients with mCRC from a US payer's perspective.

MATERIALS AND METHODS:

A partitioned survival model (PSM) was constructed to estimate total costs and quality-adjusted life years (QALYs). Clinical parameters were obtained from pivotal trials of the respective therapies and incremental cost-effectiveness ratios (ICERs) were estimated to assess relative cost-effectiveness of these treatments. Model robustness was assessed using deterministic (DSA) and probabilistic sensitivity analysis (PSA). Three scenario analyses were conducted: (1) assuming equal efficacy across treatments, (2) with prior exposure to anti-vascular endothelial growth factor (VEGF) therapy, and (3) alternative clinical inputs for fruquintinib from a different clinical trial.

RESULTS:

Under the conventional willingness-to-pay (WTP) threshold in US ($150,000 per QALY gained), ReDO was cost-effective when compared with TAS-BEV and was dominant over fruquintinib. TAS-BEV was associated with an incremental QALY of 0.197 over ReDO, resulting in an ICER at $554,567 per QALY gained. The base case results were robust in DSA and PSA. Most influential parameters were treatment cost and effectiveness. In patients with prior anti-VEGF therapy, ReDO remained cost-effective compared to TAS-BEV and fruquintinib under the conventional WTP threshold.

LIMITATION:

Differences in trial populations may affect the comparability of the outcomes. Sensitivity and scenario analyses were conducted to address these limitations.

CONCLUSION:

ReDO was cost-effective compared with TAS-BEV from the US payer's perspective despite a higher QALY gain associated with TAS-BEV. ReDO was dominant over fruquintinib, consistently having a higher QALY gain and lower cost.

3,034

项与贝伐珠单抗相关的新闻（医药）

2025-09-29

·GlobeNewswire-Health Care

Outlook Therapeutics Provides Update on Type A Meeting with FDA

ISELIN, N.J., Sept. 29, 2025 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on optimizing the standard of care for bevacizumab for the treatment of retina diseases, today announced that it has completed the Type A Meeting with the U.S. Food and Drug Administration (FDA) to discuss the complete response letter (CRL) dated August 27, 2025 regarding the biologics license application (BLA) resubmission for ONS-5010, an investigational ophthalmic formulation of bevacizumab under development to treat wet AMD. Based on the discussion with the FDA, Outlook Therapeutics expects to resubmit its BLA before the end of calendar year 2025, after reviewing the agency’s feedback and meeting minutes. “We had a productive discussion with the FDA. Based on our meeting, and pending receipt of the agency’s written minutes, we plan to resubmit the BLA later this year. We remain committed to providing patients, physicians and payors in the U.S. with a safe and effective ophthalmic bevacizumab for the treatment of wet AMD,” commented Bob Jahr, Chief Executive Officer of Outlook Therapeutics. About ONS-5010/LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma) ONS-5010/LYTENAVA™ is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA™ (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the EU and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the treatment of wet AMD. In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational. In certain European Union Member States ONS-5010/LYTENAVA™ must receive pricing and reimbursement approval before it can be sold. Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina. About Outlook Therapeutics, Inc. Outlook Therapeutics is a biopharmaceutical company focused on the development and commercialization of ONS-5010/LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma) to optimize the standard of care for bevacizumab for the treatment of retina diseases. LYTENAVA™ (bevacizumab gamma) is the first ophthalmic formulation of bevacizumab to receive European Commission and MHRA Marketing Authorization for the treatment of wet AMD. Outlook Therapeutics commenced commercial launch of LYTENAVA™ (bevacizumab gamma) in Germany and the UK as a treatment for wet AMD. In the United States, ONS-5010/LYTENAVA™ (bevacizumab-vikg) is investigational. If approved in the United States, ONS-5010/LYTENAVA™, would be the first approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD. Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “expect,” “intend,” “may,” “on track,” “plan,” “potential,” “seek,” “target,” “will,” or “would” the negative of terms like these or other comparable terminology, and other words or terms of similar meaning. These include, among others, plans to resubmit the BLA for ONS-5010 and the expected timing thereof, Outlook Therapeutics’ ability to provide the additional clarity required by the FDA’ and to address the deficiency identified in the CRL, the potential to obtain FDA approval for ONS-5010, the potential of ONS-5010/LYTENAVA™ as a treatment for wet AMD, and other statements that are not historical fact. Although Outlook Therapeutics believes that it has a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting Outlook Therapeutics and are subject to risks, uncertainties and factors relating to its operations and business environment, all of which are difficult to predict and many of which are beyond its control. These risk factors include those risks associated with developing and commercializing pharmaceutical product candidates, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals, including the risk that the Outlook Therapeutics is unable to address the issues identified in the CRL and ultimately obtain FDA approval, the content and timing of decisions by regulatory bodies, the sufficiency of Outlook Therapeutics’ resources, as well as those risks detailed in Outlook Therapeutics’ filings with the Securities and Exchange Commission (the SEC), including the Annual Report on Form 10-K for the fiscal year ended September 30, 2024, filed with the SEC on December 27, 2024, as supplemented by the Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2025 and future reports Outlook Therapeutics files with the SEC, which include uncertainty of market conditions and future impacts related to macroeconomic factors, including as a result of the ongoing overseas conflicts, tariffs and trade tensions, fluctuations in interest rates and inflation and potential future bank failures on the global business environment. These risks may cause actual results to differ materially from those expressed or implied by forward-looking statements in this press release. All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Outlook Therapeutics does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law. Investor Inquiries:Jenene ThomasChief Executive OfficerJTC Team, LLCT: 908.824.0775OTLK@jtcir.com

上市批准

2025-09-29

·信达生物

信达生物双星产品亮相2025中国卫生健康科技发展大会

9月27日上午，以“优化科研生态，加快医学创新”为主题的2025中国卫生健康科技发展大会在上海盛大开幕。信达生物携肿瘤领域核心产品信迪利单抗与代谢领域创新产品玛仕度肽亮相大会，凭借突出的临床价值与创新成果，获得与会领导、专家的高度关注与肯定。作为汇聚政产学研医多方力量的行业盛会，本次大会除开幕式及主论坛外，还设置15个分会场及科技成果展览，旨在总结“十四五”卫生健康科技创新成就、建言“十五五”卫生健康科技规划，探索“新型举国体制”下卫生健康科技创新的新路径与项目组织管理新模式。信达生物展台凭借两款重磅产品的临床突破与社会价值，成为会前领导巡展的重点关注对象。期间，陈竺院士、钟南山院士、国家卫健委副主任曾益新等领导和嘉宾来到信达生物展板前，认真听取信达生物高级副总裁高堃关于玛仕度肽与信迪利单抗的产品汇报，深入了解两款产品的研发进展、临床疗效及应用情况。在肿瘤治疗领域，信迪利单抗是目前中国PD-1抑制剂的第一大品牌，已获批八大适应症。作为中国首个获批胃癌治疗的本土创新肿瘤免疫疗法，信迪利单抗联合化疗于2022年6月获中国药监局批准，用于一线治疗不可切除的局部晚期、复发或转移性胃及胃食管交界处腺癌；2023年3月，其成为胃癌领域首个纳入国家医保的抗PD-1治疗药物，大幅降低患者用药负担；同年12月，其胃癌注册临床研究荣登国际顶级医学期刊《JAMA》主刊，2024年11月更入选“2023-2024年度中国消化道领域十佳临床研究”。临床数据显示，信迪利单抗可为PD-L1高表达胃癌患者带来19.2个月的中位总生存期（MOS），刷新胃癌治疗生存记录。陈竺院士在了解相关成果后强调，高度赞赏信迪利单抗年费仅为美国同类产品的1/30，惠及了广大肿瘤患者。在代谢疾病治疗领域，玛仕度肽以“中国方案”助力国家“体重管理年”行动。当前中国成年居民超重或肥胖率已突破50%，人数居全球首位，代谢疾病防控形势严峻。玛仕度肽的III期临床研究GLORY-1，是中国人群中评估其有效性和安全性的随机、双盲、安慰剂对照研究，于2025年5月登顶国际顶级期刊《新英格兰医学杂志》（NEJM），这也是中国代谢和内分泌领域创新药临床研究成果首次发表于该全球权威期刊，标志中国药物研发能力迈上新台阶。研究数据显示，玛仕度肽6mg治疗48周，可使患者体重较基线降低14.84%，肝脏脂肪含量下降80.2%，腰围平均减少11cm，同时显著改善血糖、血压、血脂、血尿酸等多重代谢指标。2025年6月，玛仕度肽获批用于成人长期体重控制，其更适配中国人内脏脂肪高的特点，为超重/肥胖治疗提供“中国方案”，也为国家“体重管理年”行动注入新动能。陈竺院士对玛仕度肽的优异疗效表示肯定，并关切询问其纳入医保的政策情况；钟南山院士则鼓励企业积极关注药品上市后长期使用中的疗效与安全性，为患者提供更持久的健康保障。此次亮相2025中国卫生健康科技发展大会，既是行业对信达生物创新实力的认可，也是对中国本土原研药价值的肯定。未来，信达生物将持续深耕肿瘤与代谢等重大疾病领域，以临床需求为导向，推进更多创新药物研发与应用，为优化科研生态、加快医学创新贡献企业力量，助力健康中国建设。关于信达生物 - 滑动查看更多介绍 - “始于信，达于行”，开发出老百姓用得起的高质量生物药，是信达生物的使命和目标。信达生物成立于2011年，致力于研发、生产和销售肿瘤、自身免疫、代谢、眼科等重大疾病领域的创新药物，让我们的工作惠及更多的生命。公司已有16个产品获得批准上市，它们分别是信迪利单抗注射液（达伯舒®），贝伐珠单抗注射液（达攸同®），阿达木单抗注射液（苏立信®），利妥昔单抗注射液（达伯华®），佩米替尼片（达伯坦®），奥雷巴替尼片（耐立克®），雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®），伊基奥仑赛注射液（福可苏®），托莱西单抗注射液（信必乐®），氟泽雷塞片（达伯特®），匹妥布替尼片(捷帕力®)，己二酸他雷替尼胶囊（达伯乐®），利厄替尼片（奥壹新®），替妥尤单抗N01注射液（信必敏®）和玛仕度肽注射液（信尔美®）。目前，同时还有2个品种在NMPA审评中，4个新药分子进入III期或关键性临床研究，另外还有15个新药品种已进入临床研究。公司已与礼来、罗氏、赛诺菲、Incyte和MD Anderson 癌症中心等国际合作方达成30多项战略合作。信达生物在不断自研创新药物、谋求自身发展的同时，秉承经济建设以人民为中心的发展思想。多年来，始终心怀科学善念，坚守“以患者为中心”，心系患者并关注患者家庭，积极履行社会责任。公司陆续发起、参与了多项药品公益援助项目，让越来越多的患者能够得益于生命科学的进步，买得到、用得起高质量的生物药。截至目前，信达生物患者援助项目已惠及20余万普通患者，药物捐赠总价值36亿元人民币。信达生物希望和大家一起努力，提高中国生物制药产业的发展水平，以满足百姓用药可及性和人民对生命健康美好愿望的追求。详情请访问公司网站：www.innoventbio.com或公司领英账号：Innovent Biologics。声明： 1.信达不推荐任何未获批的药品/适应症使用。 2.雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®）和匹妥布替尼片（捷帕力®）由礼来公司研发。前瞻性声明本新闻稿所发布的信息中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用“预期”、“相信”、“预测”、“期望”、“打算”及其他类似词语进行表述时，凡与本公司有关的，均属于前瞻性表述。本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述是基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些是超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。本公司、本公司董事及雇员代理概不承担 (a) 更正或更新本网站所载前瞻性表述的任何义务;及 (b) 若因任何前瞻性表述不能实现或变成不正确而引致的任何责任。

免疫疗法临床3期

2025-09-27

·BioDialectics

中国科大系统阐述ADC与ICI联合治疗的协同机理

免疫检查点抑制剂（ICIs）的出现开启了肿瘤免疫治疗的新纪元，但单药治疗仅对约20%-30%的患者有效，耐药性与“冷肿瘤”微环境（免疫细胞浸润少、免疫抑制细胞富集）是主要瓶颈。而抗体药物偶联物（ADCs）虽能精准递送细胞毒性载荷，却受限于肿瘤异质性与免疫抑制微环境。 ADC通过靶向杀伤释放肿瘤相关抗原（TAAs）与损伤相关分子模式（DAMPs），为ICI激活免疫应答提供“原料”。而ICI通过阻断PD-1/PD-L1等通路，解除T细胞耗竭，放大ADC诱导的免疫应答。二者形成“杀伤-抗原释放-免疫激活-再杀伤”的正向循环，实现1+1>2的治疗效果。一：ADC重塑TME的“三步免疫激活” ADC并非单纯的“靶向化疗药”，其杀伤肿瘤细胞的过程可激活天然免疫与适应性免疫，为ICI发挥作用奠定基础，具体分为三个关键步骤： 1.第一步：抗体依赖的细胞毒性（ADCC）启动天然免疫 ADC的抗体部分通过Fcγ受体（FcγR）激活自然杀伤（NK）细胞与巨噬细胞，NK细胞通过ADCC直接裂解肿瘤细胞，同时释放穿孔素、颗粒酶B等细胞毒性分子，进一步扩大肿瘤杀伤。肿瘤细胞裂解后释放高迁移率族蛋白1（HMGB1）、ATP、钙网蛋白（CRT）等DAMPs—HMGB1通过TLR4/NF-κB通路激活树突状细胞（DCs），ATP激活NLRP3炎症小体促进IL-1β分泌，CRT则增强DCs的吞噬能力与抗原提呈效率。NK细胞通过裂解FOXP3+Tregs、分泌TNF-α抑制MDSCs，初步瓦解TME的免疫抑制屏障。 2.第二步：免疫原性细胞死亡（ICD）激活适应性免疫 ADC诱导的肿瘤细胞死亡并非“沉默死亡”，而是具有免疫原性的ICD，其核心作用是促进T细胞活化：DAMPs激活的DCs（尤其是Batf3依赖的CD103+DCs）吞噬TAAs后，迁移至肿瘤引流淋巴结，将抗原交叉提呈给CD8+T细胞，生成肿瘤特异性细胞毒性T淋巴细胞（CTLs）。而肿瘤细胞裂解释放的线粒体DNA（mtDNA）激活DCs的cGAS-STING通路，诱导I型干扰素（IFN-α/β）分泌，进一步促进DCs成熟与CTLs增殖。同时DCs分泌的CXCL9/CXCL10等趋化因子，招募CTLs与效应CD4+T细胞进入TME，为ICIs激活免疫应答提供“细胞基础”。 3.第三步：IFN-γ诱导PD-L1上调，创造ICI治疗窗口 ADC激活的CTLs与NK细胞分泌IFN-γ，虽会通过JAK-STAT通路诱导肿瘤细胞、DCs、MDSCs上调PD-L1，形成“适应性耐药”，但这一过程也为ICIs提供了靶向靶点—PD-L1的上调使原本PD-L1阴性的肿瘤细胞变为ICIs的“敏感靶标”，实现“耐药信号向治疗机会的转化”。二：ADC-ICI协同的“时空动态调控” ADC与ICI的协同效应并非简单叠加，而是依赖精确的时空动态匹配，其关键在于“抗原释放”与“免疫激活”的时序协调： 1.空间异质性：从“免疫荒漠”到“激活hubs” ADC因分子量较大，优先在肿瘤血管周围聚集，释放DAMPs并激活NK细胞与DCs，形成“免疫激活hubs”。ADC联合抗血管生成药物（如贝伐珠单抗）可正常化肿瘤血管，降低间质压，促进ADC与CTLs向缺氧“免疫荒漠区”渗透。空间转录组分析显示，PD-L1在肿瘤浸润边缘（TME与正常组织交界处）呈“界面型表达”，此类区域CTLs浸润最多，ADC-ICI联合治疗响应最佳。而PD-L1在基质中“弥散型表达”则提示免疫抑制，需调整治疗策略。 2.时间动态：“ADC启动→ICI激活”的最佳时序早期（0-7天），ADC通过ADCC与ICD释放TAAs与DAMPs，激活天然免疫，此阶段若过早使用ICIs，可能因免疫细胞未充分激活导致效果不佳。中期（7-14天），DCs完成抗原提呈，CTLs开始浸润TME，且PD-L1因IFN-γ诱导上调，此时启动ICIs可最大程度激活CTLs，阻断PD-L1介导的免疫抑制。晚期（14天后），ICI维持CTLs活性，ADC持续清除残留肿瘤细胞，二者协同诱导TCF1+记忆T细胞生成，延长抗肿瘤免疫。曲妥珠单抗deruxtecan（T-DXd，HER2ADC）联合帕博利珠单抗（PD-1抑制剂）治疗HER2-low实体瘤，客观缓解率（ORR）达45.3%，显著高于T-DXd单药（37.1%）。KEYNOTE-355试验帕博利珠单抗联合化疗治疗PD-L1+（CPS≥10）三阴性乳腺癌（TNBC），中位无进展生存期（mPFS）达9.7个月，而单纯化疗组仅为5.6个月。当联合Sacituzumab govitecan（TROP2ADC）时，ORR进一步提升至58.2%。三：协同机制的“分子调控网络” ADC与ICI的协同作用通过多维度调控TME实现，核心机制可归纳为三大网络： 1.抗原释放-免疫激活网络 ADC杀伤肿瘤细胞释放TAAs，包括肿瘤相关抗原（如HER2胞外域）与新抗原，DCs交叉提呈后激活多克隆CTLs，扩大抗肿瘤免疫的“抗原谱”。而ICIs激活的CTLs识别TAAs后，进一步杀伤邻近肿瘤细胞，释放更多抗原，形成“免疫扩散循环”，尤其对ADC无法覆盖的抗原阴性细胞有效。单细胞TCR测序显示，ADC-ICI联合治疗后，患者外周血与TME中肿瘤特异性CTLs克隆扩增率提升3-5倍，且高亲和力CTLs比例显著增加。 2.免疫抑制解除网络 ADC激活的NK细胞通过FOXP3剪切耗竭Tregs，同时分泌TNF-α通过TNFR2信号抑制MDSCs。ICI则通过解除T细胞耗竭，增强CTLs对Tregs的杀伤。 ADC的Fc段与巨噬细胞FcγR结合，诱导其向M1型极化（分泌iNOS、ROS），增强肿瘤杀伤。ICIs进一步抑制M2型巨噬细胞分泌的IL-10、TGF-β，阻断免疫抑制。 ADC减少肿瘤细胞的葡萄糖、谷氨酰胺消耗，缓解TME的“营养剥夺”。ICIs激活的CTLs通过上调GLUT1改善自身代谢，维持antitumor活性。 3.信号通路协同网络 ADC诱导的ICD激活cGAS-STING通路，促进I型IFN分泌。ICIs激活的CTLs分泌IFN-γ，进一步增强STING通路激活，形成“信号放大环”。 ADC通过IFN-γ诱导PD-L1上调，为ICIs提供“可靶向靶点”。ICIs则阻断PD-1/PD-L1结合，解除T细胞耗竭，同时减少IFN-γ诱导的适应性耐药。 ADC释放的DAMPs激活NF-κB通路，促进趋化因子（CXCL9、CXCL10）分泌，招募免疫细胞。ICIs则通过抑制T细胞耗竭，避免过度炎症引发的免疫相关副反应事件（irAEs）。四：IMER框架—精准联合治疗的“导航系统” 为解决ADC-ICI联合治疗中的患者选择、时序优化与毒性管理问题，研究提出免疫微环境重编程（IMER）框架，通过多维度生物标志物整合，实现精准治疗： 1.血清生物标志物：动态监测治疗响应 HMGB1反映ADC诱导的ICD程度，治疗早期（7天内）HMGB1升高>2倍提示ICD激活充分，预测联合治疗响应率提升。CXCL9/CXCL10持续升高（>14天）提示免疫细胞浸润充足，与mPFS正相关。可溶性ST2（sST2）是IL-33/ST2通路标志物，sST2升高>5倍提示irAEs风险增加（如肺炎、结肠炎），需调整剂量。 2.空间生物标志物：解析TME异质性 “界面型”PD-L1（肿瘤浸润边缘高表达）提示ICIs响应良好，而“弥散型”PD-L1（基质中高表达）提示免疫抑制，需联合抗血管生成药物改善TME。TCF1+记忆T细胞比例>15%则提示长期免疫记忆形成，mOS显著延长。PD-1hiTIM-3+耗竭T细胞比例>30%则提示需调整ICI给药时序。通过单细胞空间测序，定位“免疫激活hubs”（CD8+T细胞与DCs共定位区域）与“免疫荒漠区”（MDSCs富集区域），指导ADC剂量与ICI给药部位。 3.液体活检标志物：早期预测耐药治疗2周内ctDNA清除>50%提示ADC杀伤有效，若ctDNA持续阳性（>4周），需调整ADClinker类型或载荷。外周血TCR克隆多样性增加>3倍则提示免疫激活充分，若克隆多样性下降则提示免疫耗竭，需联合IL-2等免疫激动剂。而外泌体PD-L1升高>2倍提示适应性耐药，需提前加用ICIs或更换PD-L1抑制剂。挑战与方向尽管ADC-ICI联合治疗展现出显著潜力，仍需解决三大关键问题： 1.毒性管理：平衡疗效与安全性 ADC可能引发中性粒细胞减少，ICI可能导致骨髓抑制，联合时需监测血常规，必要时使用粒细胞集落刺激因子（G-CSF）。ADC激活的NK细胞与ICIs激活的T细胞均可能分泌IL-6，引发CRS，需提前使用IL-6受体拮抗剂（托珠单抗）。可以采用“序贯给药”（ADC治疗2周后启动ICIs）可使irAEs发生率降低40%，同时不影响疗效。 2.下一代药物设计：增强协同效应设计双功能ADC，同时靶向肿瘤抗原与免疫抑制分子的ADC（如HER2/PD-L1双靶点），在杀伤肿瘤的同时阻断免疫抑制。另外设计ICIs-ADC偶联物：将ICIs作为“载荷”偶联至ADC（如抗PD-L1-微管抑制剂ADC），实现TME局部ICIs富集，减少全身毒性。也可以选择具有ICD活性的载荷（如PBD二聚体、拓扑异构酶I抑制剂），增强ADC的免疫激活能力。 3.生物标志物标准化结合基因组（TMB、MSI）、转录组（IFN-γ信号评分）与蛋白组（PD-L1、CXCL10），建立“联合响应评分”，提高预测准确性。同时通过连续液体活检（每2-4周）与影像学（PET-CT评估TILs浸润），实时调整治疗方案，避免过度治疗。总结思考 ADC与ICI的联合治疗并非简单的“1+1”，而是通过重塑TME实现“靶向杀伤-免疫激活-记忆形成”的完整抗肿瘤周期。其核心突破在于破解“冷肿瘤”困境和克服耐药性同时IMER框架通过多维度生物标志物，实现患者分层、时序优化与毒性管理。未来，随着双功能ADC、空间转录组技术的发展，ADC-ICI联合治疗将进一步向“个性化”迈进—针对不同肿瘤亚型（如TNBC、胰腺癌）设计专属联合方案，同时通过AI整合多组学数据，实现“动态调整-疗效最大化-毒性最小化”的治疗目标。这一策略不仅为难治性癌症提供新选择，更重新定义了肿瘤治疗的“协同范式”，推动免疫治疗从“广谱激活”向“精准调控”转型。 Reprogramming the tumor microenvironment: synergistic mechanisms of antibody-drug conjugates and immune checkpoint inhibitors. Antib Ther. 2025 Sep 17;8(3):262-274. doi: 10.1093/abt/tbaf017. eCollection 2025 Jul.

抗体药物偶联物免疫疗法

100 项与贝伐珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06409	贝伐珠单抗	L01XC07	DB00112

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
不可切除的肝细胞癌	日本	Chugai Pharmaceutical Co., Ltd.	2020-09-25
肝细胞癌	美国	Genentech, Inc.	2020-05-29
复发性胶质母细胞瘤	美国	Genentech, Inc.	2020-05-29
复发性原发性腹膜癌	美国	Genentech, Inc.	2014-11-14
卵巢癌	日本	Chugai Pharmaceutical Co., Ltd.	2013-11-22
胶质瘤	日本	Chugai Pharmaceutical Co., Ltd.	2013-06-14
乳腺癌	日本	Chugai Pharmaceutical Co., Ltd.	2011-09-26
结直肠癌	日本	Chugai Pharmaceutical Co., Ltd.	2009-09-18
转移性肾细胞癌	美国	Genentech, Inc.	2009-07-31
胶质母细胞瘤	美国	Genentech, Inc.	2009-05-05
转移性结直肠癌	美国	Genentech, Inc.	2009-05-05
节细胞神经胶质瘤	日本	Chugai Pharmaceutical Co., Ltd.	2007-04-18
非鳞状非小细胞肺癌	美国	Genentech, Inc.	2006-10-11
输卵管癌	欧盟	Roche Registration GmbH	2005-01-12
输卵管癌	冰岛	Roche Registration GmbH	2005-01-12
输卵管癌	列支敦士登	Roche Registration GmbH	2005-01-12
输卵管癌	挪威	Roche Registration GmbH	2005-01-12
转移性乳腺癌	欧盟	Roche Registration GmbH	2005-01-12
转移性乳腺癌	冰岛	Roche Registration GmbH	2005-01-12
转移性乳腺癌	列支敦士登	Roche Registration GmbH	2005-01-12

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
晚期子宫内膜癌	临床3期	-	National Cancer Institute	2025-12-15
复发性子宫内膜癌	临床3期	-	National Cancer Institute	2025-12-15
晚期头颈癌	临床3期	美国	National Cancer Institute	2023-03-13
头颈部皮肤鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-03-13
头颈癌转移	临床3期	美国	National Cancer Institute	2023-03-13
鼻咽癌	临床3期	美国	National Cancer Institute	2023-03-13
鼻咽鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-03-13
口咽肿瘤	临床3期	美国	National Cancer Institute	2023-03-13
复发性咽部鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-03-13
复发性头颈部鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-03-13

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临床结果

适应症

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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


NCT04487067 (AMETHISTA, CTgov)	临床3期	不可切除的肝细胞癌	152	Atezolizumab+Bevacizumab	壓願積獵積遞鬱糧淵艱 = 糧鑰蓋獵鏇獵構簾網簾餘糧廠蓋壓選膚壓蓋衊 (衊淵憲築鹽淵夢蓋獵製, 鹽願願鬱夢範顧選鑰窪 ~ 淵鏇遞膚襯積憲繭鹹築) 更多	-	2025-09-22
NEWS 人工标引	临床2期	非鳞状非小细胞肺癌	-	斯鲁利单抗+贝伐珠单抗+培美曲塞+卡铂	製鏇顧繭鬱醖餘衊積齋(鹹遞鹽遞齋齋鹽廠醖顧) = 獵製鬱膚築襯鑰繭齋簾艱餘獵遞齋鑰築艱艱構 (繭齋鹽繭憲憲築鹹窪觸 ) 更多	积极	2025-09-10
NCT04958811 (WCLC2025)	临床2期	鳞状细胞肺癌二线 PDL1 TPS ≥1%	12	bevacizumab+Atezolizumab+Tiragolumab	鏇憲餘鏇網積網膚選鏇(鹹淵鹹蓋觸淵餘餘觸窪) = 衊鏇觸糧築餘蓋鏇鹹積襯壓鹽壓襯蓋鑰壓範構 (積構淵鑰憲簾齋製遞廠 ) 更多	积极	2025-09-07
EURETINA2025	N/A	葡萄膜脑膜脑炎综合征	9	Ranibizumab	齋繭獵淵鑰網選膚齋願(鬱窪糧夢齋網鹽糧繭衊) = 築鹽選鑰範遞簾築顧積衊遞餘範鹹築繭顧窪鹹 (遞積鏇醖製鬱蓋範遞觸 ) 更多	积极	2025-09-04
NCT02681549 (Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases, CTgov)	临床2期	非小细胞肺癌 \| 转移性黑色素瘤 \| 鳞状非小细胞肺癌 ... 更多	41	Pembrolizumab+Bevacizumab (Untreated Brain Metastases From Melanoma)	廠選鹹醖廠壓築積襯衊 = 壓衊廠積窪蓋襯構選醖襯獵齋積簾糧糧壓鏇齋 (鏇餘選鹽製鏇鹹蓋鹹壓, 壓壓鏇鹹選憲構憲獵膚 ~ 艱憲糧構鹽憲鏇糧獵觸) 更多	-	2025-08-07
	临床2期	非小细胞肺癌 \| 转移性黑色素瘤 \| 鳞状非小细胞肺癌 ... 更多	41	Pembrolizumab+Bevacizumab (Untreated Brain Metastases From NSCLC)	廠選鹹醖廠壓築積襯衊 = 願範觸網壓顧齋顧製夢襯獵齋積簾糧糧壓鏇齋 (鏇餘選鹽製鏇鹹蓋鹹壓, 構衊獵簾廠夢餘繭選鹹 ~ 窪網選蓋衊廠憲鬱鏇選) 更多	-	2025-08-07
NCT05357417 (U-BOMB, Pubmed \| JAMA Oncol) 人工标引	临床2期	转移性HER2阴性乳腺癌 HER2/Neu Negative	47	Utidelone +Bevacizumab	醖艱獵積壓顧範鏇窪願(積鏇艱鏇鬱醖範繭遞膚) = 觸觸獵構鹹醖網願齋壓憲夢醖願鹹構範糧鏇衊 (鹽齋觸築憲壓範醖衊鹹, 28.3 ~ 57.8) 更多	积极	2025-08-01
DUBHE-L-201 (Pubmed \| J Hematol Oncol) 人工标引	临床2期	EGFR突变的非小细胞肺癌 EGFR Mutation	31	Iparomlimab and tuvonralimab (QL1706) + Bevacizumab + Chemotherapy (cohort 5)	選鏇衊範廠積廠糧鏇膚(廠鬱淵積淵積鏇遞繭簾) = 簾鹽窪構鑰廠簾繭鏇夢遞選願鹽鑰構獵選淵壓 (齋簾醖製窪窪築齋壓齋, 12.81 ~ NR) 更多	积极	2025-07-26
DUBHE-L-201 (Pubmed \| J Hematol Oncol) 人工标引	临床2期	EGFR突变的非小细胞肺癌 EGFR Mutation	31	Iparomlimab and tuvonralimab (QL1706) + Bevacizumab + Chemotherapy (21L858R mutation + cohort 5)	選鏇衊範廠積廠糧鏇膚(廠鬱淵積淵積鏇遞繭簾) = 壓築鑰製壓醖繭鹽範糧遞選願鹽鑰構獵選淵壓 (齋簾醖製窪窪築齋壓齋 ) 更多	积极	2025-07-26
NCT03574779 (OPAL Phase II Trial \| OPAL, CTgov)	临床2期	卵巢癌	77	Niraparib+Bevacizumab+Dostarlimab (Cohort A (Dostarlimab + Bevacizumab + Niraparib))	淵製鏇鬱願觸蓋鹹簾餘 = 淵餘鏇膚夢築簾壓齋淵襯觸衊網築積網觸壓淵 (襯窪窪選選窪鑰廠築積, 衊鬱築獵鑰築糧鏇壓網 ~ 衊窪獵製齋鏇網壓網網) 更多	-	2025-07-15
NCT03574779 (OPAL Phase II Trial \| OPAL, CTgov)	临床2期	卵巢癌	77	taxane+Niraparib (Cohort C (Niraparib OR Platinum-taxane))	淵製鏇鬱願觸蓋鹹簾餘 = 築鹹觸構壓鏇觸醖膚顧襯觸衊網築積網觸壓淵 (襯窪窪選選窪鑰廠築積, 膚艱艱糧醖鹽廠積築淵 ~ 積鏇艱壓夢夢製壓廠齋) 更多	-	2025-07-15
NCT04712643 (TALENTACE, NEWS \| ASCO_GI2025) 人工标引	临床3期	不能切除的恶性肝癌	342	TACE+阿替利珠单抗+贝伐珠单抗	鏇蓋壓淵積簾構蓋膚餘(網衊壓簾糧繭獵鏇簾壓) = 夢餘廠構窪蓋齋艱遞餘構觸艱夢構鑰構築顧糧 (網鹽憲遞鬱網淵壓範壓 ) 更多	积极	2025-07-04
NCT04712643 (TALENTACE, NEWS \| ASCO_GI2025) 人工标引	临床3期	不能切除的恶性肝癌	342	单独TACE	鏇蓋壓淵積簾構蓋膚餘(網衊壓簾糧繭獵鏇簾壓) = 網鹹衊夢夢獵選糧襯襯構觸艱夢構鑰構築顧糧 (網鹽憲遞鬱網淵壓範壓 ) 更多	积极	2025-07-04
NCT04732286 (ATHECA, ESMO_GI2025) 人工标引	临床3期	不可切除的肝细胞癌一线	100	Atezolizumab + Bevacizumab	夢膚壓獵築蓋膚淵願繭(積衊積積願簾積糧觸鹽) = 窪積鑰襯壓獵範醖蓋構淵齋構築繭積範積壓鏇 (鹽膚遞顧鬱顧構選範鏇 ) 更多	积极	2025-07-03