A Multicenter Phase I/II Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel With or Without NPC-1C in Patients With Metastatic or Locally Advanced Pancreatic Cancer Previously Treated With FOLFIRINOX

This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C).
The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. .
In the Phase 2 portion patients were randomized into one of two arms:
A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel

开始日期2013-04-01

申办/合作机构

Precision Biologics, Inc.

NCT01040000

/ Completed临床1/2期

A Phase 1/2 Therapeutic, Open Label, Multi-Center Clinical Trial of NPC-1C, a Chimeric Monoclonal Antibody, in Adults With Recurrent, Locally Advanced Unresectable or Metastatic Pancreatic and Colorectal Cancer After Standard Therapy

The purpose of the phase 2 component of this study is to determine if giving the immune molecule NPC-1C to individuals who have cancer of the pancreas or gastrointestinal tract (colon or rectum) which has not responded to standard treatments can shrink or halt the growth of cancer, and to obtain additional data to study its effect on the immune system. Safety data will also be accumulated and evaluated during this study. NPC-1C is a monoclonal antibody that recognizes a specific tumor target on certain cancers. In laboratory studies, the antibody killed tumor cells in some colon and pancreatic cancers that express the NPC-1C antigen by a process called "antibody-dependent cell cytotoxicity" or ADCC.

开始日期2012-01-01

申办/合作机构

Precision Biologics, Inc.

ACTRN12607000448448

/ Active, not recruiting临床2期

A Phase 2 Two-Center, Randomized, Double-blind, Placebo-controlled, Paired Treatment Site Comparison Study to Evaluate the Safety and Preliminary Efficacy of a Topical Antimicrobial (NEO101) in Reduction of Wound Bioburden among Adults Treated with Curettage & Electrodessication for Superficial Basal Cell Carcinomas of the Trunk and Extremities

开始日期2007-09-10

申办/合作机构

Neosil, Inc.

100 项与 Ensituximab 相关的临床结果

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100 项与 Ensituximab 相关的转化医学

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100 项与 Ensituximab 相关的专利（医药）

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项与 Ensituximab 相关的文献（医药）

2020-07-15·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

1区 · 医学

Article

作者: Azad, Nilofer S. ; Tan, Benjamin ; Beg, Muhammad S. ; Tsang, Kwong Y. ; Arlen, Philip M. ; Zaki, Anjum ; Morse, Michael A. ; Torrealba, Jose ; Kim, Richard D. ; Mahipal, Amit ; Poplin, Elizabeth ; Mavroukakis, Sharon A. ; Fantini, Massimo

Abstract:

Purpose::

Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer.

Patients and Methods::

Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients.

Results::

Sixty-three patients with advanced, refractory colorectal cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs.

Conclusions::

Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer.

2016-09-01·Cancer chemotherapy and pharmacology4区 · 医学

A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer

4区 · 医学

Article

作者: Wang, Xue Ping ; Arlen, Philip M ; Beg, Muhammad S ; Torrealba, Jose ; Azad, Nilofer S ; Morse, Michael A ; Beatson, Melony A ; Patel, Sandip P ; Mavroukakis, Sharon

PURPOSE:

NEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity.

METHODS:

This is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg.

RESULTS:

A total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer.

CONCLUSIONS:

Treatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies.

2014-03-10·JOP : Journal of the pancreas

Novel agents for the treatment of pancreatic cancer.

作者: Gregory T Brennan ; Valerie Relias ; Muhammad Wasif Saif

Metastatic pancreatic cancer continues to be a difficult disease to treat because of its aggressive nature, advanced stage at presentation and lack of treatment options. There is a need for the development of new agents directed against novel targets to improve outcomes for these patients. At the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium phase I/II trials provided information on three novel strategies for treating metastatic pancreatic cancer. Immunotherapy in the form of a vaccine (GVAX) followed with an immune stimulator (CRS-207) showed extended survival (Abstract #177). A monoclonal antibody (NEO-102) targeting MUC5AC also showed activity and was well tolerated (Abstract #243). A heat shock protein 90 (HSP90) inhibitor (ganetespib) showed modest effects but was well tolerated making it available for use with conventional chemotherapy (Abstract #297). The details of these presentations will be discussed.

项与 Ensituximab 相关的新闻（医药）

2024-11-06

·PRNewswire

Precision Biologics to Announce Development of New Monoclonal Antibody (mAb) PB-223 at SITC, Houston, TX, November 7-8, 2024

Precision Biologics will present affinity maturation and characterization of a novel core 2 O-glycan epitope targeting anti-human carcinoma mAb PB-223 at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024 BETHESDA, Md., Nov. 6, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that affinity maturation and characterization of its novel anti-core 2 O-glycan monoclonal antibody PB-223, will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024, George R. Brown Convention Center, Houston, Texas, USA, Poster title: Affinity Maturation and Characterization of a Novel O-glycan Epitope Targeting Anti-Human Carcinoma Monoclonal Antibody (mAb) PB-223 Presentation of the poster will be made in person on the following dates and locations: November 7th, 2024: SITC Immune Engineering Workshop, 3.10 p.m-5 p.m. CST, George R. Brown Convention Center, Level 3 - Grand Ballroom AB, Houston, Texas, USA November 8th, 2024: Poster Session Immuno-Engineering, abstract number 1101, 12:15–1:45 p.m. CST and 5:30-7 p.m. CST, George R. Brown Convention Center, Level 1-Exhibit Halls A B, Houston, Texas, USA BACKGROUND: PB-223 is an innovative mAb developed through immune engineering from the chimeric IgG1 NEO-102 (Ensituximab). It targets a unique core 2 O-glycan (variant of MUC5AC), Preclinical and clinical data showed that NEO-102 specifically binds to and kills colorectal and pancreatic cancer cells through ADCC. NEO-102 did not bind to healthy tissues. In a phase 2 study, NEO-102 showed promising results in heavily pretreated patients with advanced, refractory metastatic colorectal cancer. In general, the efficacy of using a monoclonal antibody as a single agent in cancer immunotherapy can be impaired not only by the resistance of cancer cells in the tumor microenvironment (TME), but also by a low binding affinity to target antigens expressed on cancer cells. One strategy to improve the therapeutic efficacy of monoclonal antibodies is to enhance their binding affinity to target antigens. STUDY PRESENTED AT SITC 2024: The objective of this study was to enhance the binding affinity of NEO-102 to its target antigen. By engineering the VH and VL sequences of NEO-102 through Fast Screening for Expression Biophysical Properties and Affinity (FASEA), while maintaining the binding specificity to the target antigen, allowed us to develop a new clone with a lower KD and markedly improved characteristics. This new biologic asset developed by affinity maturation was given the name PB-223. Binding kinetics of PB-223 and NEO-102 to the target antigen were compared by ELISA. Results show that PB-223 has a KD of 4.5-fold less than NEO-102, suggesting a higher affinity for the target antigen by PB-223 compared to NEO-102. The binding affinity of PB-223 and NEO-102 to various human tumor cell lines was also evaluated by flow cytometry. Flow cytometry analysis showed that PB-223 not only has markedly enhanced comparative binding to colorectal and pancreatic cancer cell lines recognized by NEO-102, but that PB-223 is also able to bind to many additional tumor cell lines that were not recognized by NEO-102. Further study by O-glycan array analysis showed that 1) PB-223 binds specifically to core-2 O-glycans, and that 2) core 2 O-glycans recognized by PB-223 are expressed on tumor cell lines positive for PB-223 binding in flow cytometry. Immunohistochemistry (IHC) analysis performed on human tumor tissues shows that PB-223 does not bind to healthy tissues. IHC analysis also shows that PB-223, in addition to binding to both colorectal cancer and pancreatic cancer, it also binds to additional tumor tissues not reactive with NEO-102, including triple negative breast cancer, prostate cancer, kidney cancer, head and neck cancer, liver cancer, and bladder cancer. In addition, this study demonstrated that PB-223 is internalized into human cancer cell lines expressing core 2 O-glycans. Findings from this study suggest that PB-223 has a strong binding affinity for human cancers expressing core 2 O-glycans and that PB-223 may be a potential candidate for the development of antibody-drug conjugates (ADC) for treatment of various human carcinomas. The PDF of the poster will be available starting from November 5, 2024, at the following link: SOURCE Precision Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果免疫疗法临床2期AACR会议

2022-11-22

·生物制药小编

靶向粘蛋白(Mucin)肿瘤特异性糖表位的ADC药物

寻找理想的靶向表位是开发ADC药物的关键。为了最大限度地将药物输送到肿瘤细胞并减少副作用，ADC靶向的表位应该是针对癌细胞的，而不是正常组织。在癌症进展过程中，糖基化途径经常发生改变，导致产生对癌细胞具有选择性的新的糖基化模式。粘蛋白(mucin)是一种高度糖基化的蛋白质，经常在肿瘤上表达，因此是糖表位的理想呈现者。本文我们就粘蛋白三种不同类型的糖表位，以及靶向粘蛋白肿瘤特异性糖表位的ADC药物做一个简要介绍。肿瘤中的粘蛋白粘蛋白通常是由上皮细胞膜表达的大型糖蛋白(200 kDa-200 MDa)。这一蛋白质家族的特征在于存在一个或多个富含模块化脯氨酸(Pro)、苏氨酸(Thr)、丝氨酸(Ser) (PTS)的结构域，其中高频率的Thr或Ser与α-N-乙酰半乳糖胺(α-GalNAc)部分共价结合(O-linked的糖基化)。尽管绝大多数粘蛋白聚糖属于O-linked糖类型，但也含有通过天冬酰胺(Asn)共价修饰的N-linked聚糖。聚糖通常占粘蛋白分子分子质量的80%以上，这种亲水性碳水化合物结构在改变细胞膜的生物物理性质以及其拓扑结构方面起着关键作用。粘蛋白经常在组织屏障结构的表面、脱落(蛋白水解切割)或分泌表达。它们的存在保持了这些屏障的完整性，同时也限制了与病原体、毒素和抗原以及可能引起损伤和引发炎症反应的炎症因子的接触。分泌/脱落粘蛋白可以帮助中和病原体，跨膜粘蛋白在感知环境和维持组织结构中发挥作用。肿瘤发生利用粘蛋白的功能来促进自身的生长和存活，增强运动性，限制粘附和逃避免疫监视。此外，肿瘤发展过程中粘蛋白表达失调可能伴随着糖基化和代谢机制的改变，导致异常的粘蛋白糖型，其物理和功能特性发生改变。目前有四种已在在癌症中被广泛研究的粘蛋白：MUC1、Podxl、MUC16和MUC5AC。MUC1是粘蛋白家族的初始成员，通常在各种组织的腺或腔上皮细胞上表达，其延伸的带负电荷的糖分支产生了具有抗粘附特性的选择性生物物理屏障，限制了病原体的可及性。MUC1已被证明是ADC的一个潜在靶标，因为异常糖基化的MUC1在大多数人类上皮癌中过度表达。Podxl是干细胞抗原CD34家族的高度糖基化细胞表面唾液蛋白，在正常和癌症组织中的细胞粘附和跨内皮迁移中起重要作用。它的表达在多种癌症类型中上调。Podxl的过表达与不良预后，肿瘤的侵袭性以及化疗药物耐药有关。MUC16是所有已知粘蛋白中最大的，是CA125表位的携带者，该抗原被广泛用作检测卵巢癌的血清标记物。MUC5AC是一种分泌型凝胶形成粘蛋白，通常构成气道粘液层。在癌症中，它在一系列肿瘤类型中表达上调，并且它的表达主要在细胞质中或在肿瘤细胞的表面。粘蛋白三种不同类型的糖表位糖表位是指由单克隆抗体或其他聚糖结合蛋白识别的碳水化合物部分。仅结合聚糖的单克隆抗体的亲和力通常远低于蛋白质特异性单克隆抗体， KD值通常在µM范围内。由于聚糖表位经常在蛋白质核心上串联，聚糖结合单克隆抗体的低亲和力可以通过产生具有两个或多个识别重复聚糖表位的单克隆抗体来避免，从而形成多价复合物。另一类表现出更好的结合亲和力和特异性的肿瘤相关碳水化合物抗原的结合单抗是识别由糖和已知的多肽表位组合形成的糖肽表位。它们往往表现出与蛋白质抗原相当的特异性和亲和力。第三种类型的糖表位，称之为“屏蔽糖肽表位”并不是真正的糖表位。单抗并不直接与糖结合，而是识别多肽表位，其对多肽序列的识别受到糖蛋白糖基化状态的限制。这三类表位的示意图1所示。图1. 粘蛋白三种不同类型的糖表位靶向粘蛋白肿瘤特异性糖表位的ADC虽然现在鉴定规则多肽表位的氨基酸序列相对容易，但糖表位结构的表征由于其复杂的支链结构而充满挑战性。目前大多数mAb/ADC靶标的确切糖表位结构仍不是十分清晰。靶向粘蛋白糖基的ADC糖基结合抗体的一个主要例子是小鼠JAA-F11 IgG3或人源化的hJAA-F11 H2aL2a IgG1，它结合由D-galactose-beta-(1–3)-N-acetyl galactosamine (Gal-β-(1-3)-GalNAc)与丝氨酸/苏氨酸连接形成的T抗原。T抗原是一种隐蔽的癌胎儿抗原，在癌症中经常由粘蛋白表达。与其他靶向T抗原的单抗不同，JAA-F11单抗高度特异于与肿瘤相关的α -linked T抗原，而不是表达在正常组织表面的beta-linked 结构。JAA-F11单抗是开发ADC的极佳候选者，因为它在与抗原结合后迅速内化。当与微管蛋白抑制剂DM1结合时，hJAA-F11 H2aL2a-DM1 ADC显示出对三阴性乳腺癌和肺癌细胞株的强大体外细胞毒活性，并显著减少了MDA-MB-231小鼠异种移植模型中的肿瘤生长。鉴于T抗原在肿瘤中的广泛表达，这种ADC具有巨大的治疗潜力。另一种有趣的糖链结合单抗是小鼠IgG1 FG129及其嵌合的人IgG1变异体CH129。CH129以高亲和力识别sialyl-di-Lewisa多糖以及表达在几种高分子量糖蛋白的两种密切相关的糖链：sialyl-Lewisa-Lewisx和sialyl-Lewisa。CH129偶联MMAE(CH129-MMAE)在pM至nM范围内显示出优异的体外效果。在COLO205异种移植小鼠模型中，CH129-MMAE在剂量为5 mg/kg (biweekly)时， 10只小鼠中有7只显示出有效的肿瘤生长控制和肿瘤消除。CH129糖表位在多种癌症类型上都有表达，提示其具有广阔的潜力。虽然这个表位主要是肿瘤特异性的，但FG129与胆囊、回肠、肝脏、食道、胰腺和甲状腺组织中的一小部分细胞有很弱结合，因此在临床开发过程中的off-target效应仍然是一个潜在的问题。靶向MUC1糖表位的ADC一些MUC1靶向的单抗和单链可变区(ScFv)已作为潜在的癌症治疗方法，下面我们主要介绍下靶向MUC1糖表位的ADC药物。16A是以MUC1的糖表位为靶标的小鼠IgG1。该单抗与糖肽RPAPGS(GalNAc)TAPPAHG强烈结合，但与非糖基化RPAPGSTAPPAHG的结合要弱得多(通过ELISA方法检测低25倍)。然而用表面等离子体共振(SPR)测的亲和力是相似的(KD~500-1000 nM)。肿瘤上异常糖基化的MUC1与16A具有更高的表观亲和力，这可能是由于糖链引起的构象变化，促进了单抗与其多肽表位(即屏蔽肽表位)的接触，或者16A可能同时与多肽和糖链部分进行分子间接触(即糖肽表位)。16A结合在肺癌、乳腺癌和胃癌组织上表达的靶标表位，并被迅速内化，使其成为ADC候选药物。研究发现，16A MMAE ADC，在体外可以有效地杀死肺、乳腺、胰腺、胃和卵巢细胞系。此外，在小鼠H838(非小细胞肺癌)异种移植模型中，16A MMAE ADC以剂量依赖的方式抑制肿瘤生长。Gatipotuzumab，是小鼠IgG1 PankoMab的人源化版本。这种单抗最初是为了最大限度地区分碳水化合物诱导的MUC1上的构象肿瘤表位(TA-MUC1)和非糖基化的MUC1表位。TA-MUC1表位包括…PDT*RP…氨基酸，其中T*是GalNAc α1-或类似的短的、非唾液酸化的多糖。PankoMab与其表位之间的确切相互作用位点尚不清楚，但它与TA-MUC1糖化版本的强结合以及与同一肽的非糖化版本的弱结合强烈表明PankoMab表位是糖肽表位。由于Gatipotuzumab 的ADCC活性，在2018年，Daiichi-Sankyo和Glycotope GmbH达成了一项全球独家许可协议，通过将Daiichi-Sankyo的专有ADC技术与Glycotope的gatipotuzumab相结合来开发ADC。小鼠MuDS6 IgG1 mAb单抗识别MUC1的唾液酸依赖表位(唾液酸糖基表位)，命名为“CA6”。然而，确切的糖表位结构仍有待确定，可能是糖肽表位，也可能是被屏蔽的多肽糖表位。人源化的DS6单抗以一种抗原依赖的方式有效地内化。人源化的DS6与DM4偶联生成SAR566658 ADC可诱导体外强细胞毒作用，并在多种人肿瘤细胞系小鼠模型中有效地控制了肿瘤生长。在CA6阳性转移性乳腺癌患者(NCT01156870)的I期研究中，SAR566658提供了良好的安全性和优异的抗肿瘤活性。然而，随后对转移性三阴性乳腺癌患者进行的II期研究(NCT02984683)初步分析其具有较高的眼毒性，例如角膜炎和角膜病变。虽然DS6单抗主要与肿瘤组织结合，但它们也识别一些正常的成人组织(如输卵管、肺泡和尿路上皮)，这可能会影响其用于肿瘤特异性靶向的有效性。huC242 mAb(Cantuzumab)高选择性地识别存在于MUC1癌抗原(CanAg)糖上的胞外CA242表位。表位的确切结构也尚未确定，但由于它含有唾液酸，它很可能是描述的三类糖表位之一。研究表明HuC242-DM1对 CanAg阳性的COLO205移植瘤具有强效的抗肿瘤作用，这种ADC还可以诱导旁观者效应，杀死近端抗原阴性的肿瘤细胞。在I期临床试验中，ImmunoGen与GSK合作测试了huC242-DM1 ADC(SB408075：cantuzumab mertansine)的治疗潜力，以确定最佳治疗方案和剂量毒性。在CanAg强表达的肿瘤中观察到huC242-DM1的活性。然而，与剂量相关的肝毒性阻止了剂量的进一步增加，临床实验因此而终止。与DM4偶联的huC242 DM4 ADC (IMGN242：cantuzumab ravtanstine)在人胃癌异种移植瘤小鼠中使得肿瘤完全消退。IMGN242在I期临床试验(NCT00352131)中耐受性良好。在II期试验(NCT00620607)中，在6例CanAg阳性的胃或胃食道交界处癌症患者中，1例观察到部分缓解。不幸的是，6名患者中有3名患者出现了眼部毒性。靶向其他粘蛋白糖表位的ADC最近开发了一种高度肿瘤特异性的兔/人嵌合IgG1 mAb，命名为PODO447，它可以与表达在肿瘤细胞上而不是正常组织上的Podxl结合。该mAb特异性地结合了由Podxl多肽的O-linked的聚糖（T-抗原）组成的糖肽表位。PODO447-MMAE ADC以抗原依赖的方式在各种癌细胞系中诱导体外细胞毒性。在体内，PODO447 ADC剂量在2-4 mg/kg时使得卵巢和胰腺癌肿瘤消退。目前正在进行I期实验。AR9.6是一种小鼠单抗，它结合受O糖影响的MUC16 SEA domain 5构象表位。人源化AR9.6对肿瘤细胞对的良好靶向和内吞暗示了这种ADC治疗潜力。NEO-102(Ensituximab)是一种识别MUC5AC的NPC-1C糖表位的嵌合鼠/人IgG1mAb，这是一种异常糖基化的表位，在胰腺癌和结直肠癌中优先表达。因此，NEO-102可以区分在正常组织上表达的天然MUC5AC和在肿瘤组织中表达的MUC5AC的变体。在体内小鼠模型中，未结合的NEO-102显著降低了CFPAC-1胰腺肿瘤异种移植瘤的生长。然而，在由Precision Biologics 资助的II期临床试验中，NEO-102仅在难治性转移性结直肠癌患者中显示出适度的抗肿瘤活性。但这些患者对非结合抗体治疗的耐受性很好，这表明将NEO-102与细胞毒素偶联以产生ADC或许可以安全地增加NEO-102的抗肿瘤潜力。小编小结虽然大多数靶向粘蛋白糖表位的ADC在体外和动物模型中具有强大的抗肿瘤效果，但进入临床试验的ADC到目前为止还没有发挥十分优异的效果，有些甚至显示了意想不到的副作用。有几个因素可以解释这些不佳的结果(图2)。首先，含有ADC糖表位的胞外粘蛋白结构域的脱落或分泌可以减少ADC与其靶标的特异性结合，从而降低疗效。因此在临床试验期间应仔细测量进入循环的靶表位，以评估抗原脱落影响疗效的可能性。另一个因素是糖表位的肿瘤特异性。虽然本文描述的ADC靶向的糖表位主要在癌细胞表达，但许多在正常组织细胞亚群上有较低的表达，这可能会导致显著的正常组织毒性。第三个可能的限制因素是，在治疗期间，肿瘤可能会受到选择性压力来改变它们糖基转移酶表达，使得肿瘤发生逃逸。因此，在临床前模型和临床试验期间，应尽可能的在治疗后仔细监测糖表位的表达。图2.粘蛋白糖表位ADC所面临的挑战参考文献1.Antibody-Drug Conjugates Targeting Tumor-Specific Mucin Glycoepitopes.2.Mucins in cancer: function, prognosis and therapy.3.Cancer-associated mucins: role in immune modulation and metastasis.

抗体药物偶联物

100 项与 Ensituximab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09898	Ensituximab	-	DB12342

研发状态

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
成人胰腺癌	临床2期	美国	Precision Biologics, Inc.	2013-04-01
转移性结直肠癌	临床2期	美国	Precision Biologics, Inc.	2012-01-01
转移性胰腺癌	临床2期	美国	Precision Biologics, Inc.	2012-01-01
结直肠癌	临床2期	美国	Precision Biologics, Inc.	-
结直肠癌	临床2期	-	Neogenix Oncology, Inc.	-
胰腺癌	临床2期	-	Neogenix Oncology, Inc.	-

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临床结果

适应症

分期

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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


NCT01834235 (AACR2022) 人工标引	临床2期	胰腺癌二线	80	Ensituximab+gemcitabine+Albumin-Bound Paclitaxel	構獵範選醖鏇鏇願衊顧(蓋選憲衊網糧衊糧艱構) = 齋鑰夢網鏇顧淵積鹹廠糧繭夢憲願鹹窪憲艱製 (網構壓觸構願鏇糧鬱鏇, 3.3 ~ 6.5) 更多	不佳	2022-11-15
NCT01834235 (AACR2022) 人工标引	临床2期	胰腺癌二线	80	gemcitabine+Albumin-Bound Paclitaxel	構獵範選醖鏇鏇願衊顧(蓋選憲衊網糧衊糧艱構) = 遞遞積鏇糧艱膚顧範繭糧繭夢憲願鹹窪憲艱製 (網構壓觸構願鏇糧鬱鏇, 4.7 ~ 8.4) 更多	不佳	2022-11-15
NCT01040000 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	结直肠癌	63	Ensituximab	壓積簾膚選顧艱艱顧襯(繭夢顧齋鏇遞壓繭鑰膚) = 壓鏇餘鑰鹽鏇餘鑰憲壓艱壓膚築簾構範膚齋襯 (壓繭窪鑰選築獵壓夢築 ) 更多	积极	2020-07-15
NCT01040000 (ASCO2017)	临床1/2期	结肠转移性腺癌	63	Ensituximab	襯築壓鬱繭糧壓願衊壓(膚鏇築獵鹽遞衊夢淵廠) = 鑰廠衊遞鏇構壓醖遞鏇糧膚淵襯願簾憲醖鬱鏇 (獵衊憲糧築顧願鑰壓廠, 5.39 ~ 8.02) 更多	积极	2017-05-30
NCT01040000 (NEO-102, ASCO_GI2016)	临床2期	结肠转移性腺癌	47	NEO-102	獵鑰襯網憲積餘鏇壓鏇(齋鏇築淵壓範膚構艱網) = 蓋願襯壓餘鹽廠餘鑰膚鬱遞繭鬱蓋構範製鹹齋 (選襯範遞鏇餘鹹構齋選 ) 更多	积极	2016-02-01
NCT01040000 (ASCO2015)	临床2期	难治性结直肠癌	43	NEO102 (N)	憲簾壓蓋選鹹壓窪醖鏇(構衊糧壓糧築範鹹廠構) = 鏇積衊廠襯壓醖膚鑰廠夢觸鏇繭鏇鬱網窪網餘 (選窪鏇積積遞艱築窪淵 )	-	2015-05-20
NCT01040000 (ASCO_GI2015)	临床1/2期	难治性癌症	94	NEO102	簾齋獵範醖範廠齋鬱鹹(簾齋蓋醖餘糧鏇衊膚壓) = 壓襯鏇觸鏇簾窪蓋鏇簾膚獵鹹積鹹淵獵願餘餘 (鑰鏇構淵窪夢壓鬱製膚 ) 更多	-	2015-01-20
AACR2013	临床1期	结直肠癌 \| 胰腺癌	15	NPC-1C	壓構製構鏇襯衊壓顧繭(醖鹹鏇繭餘夢衊衊衊獵) = 夢襯獵簾積壓襯構鑰範鹹醖蓋築構觸範窪鏇鑰 (夢製願鹽憲獵齋顧餘築 )	-	2013-04-15
ASCO2012	临床1期	结直肠癌 \| 胰腺癌	15	NPC-1C	簾製餘網積壓網簾糧鹹(糧襯網蓋鹽顧構網鹽繭) = 襯鬱構築鏇餘夢窪觸構夢衊網範蓋膚鹹願繭選 (夢糧壓衊糧餘網壓獵憲 )	-	2012-05-20
ASCO_GI2012	临床1/2期	结直肠癌 \| 胰腺癌	-	NPC-1C	範廠觸夢獵膚遞繭壓鬱(齋繭壓膚鏇構顧網憲鑰) = 夢製艱餘齋蓋積餘夢顧遞廠齋憲築夢觸製範鏇 (艱窪窪鏇窪遞蓋蓋夢膚 )	-	2012-02-01