ABY-029(ABY-029) - 药物靶点：EGFR_在研适应症：胶质瘤_专利_临床

概要

基本信息

药物类型

抗体光敏剂缀合物

别名

ABY-029 trifluoroacetate salt

靶点

EGFR

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、诊断染料分子

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Affibody ABLi-Cor Bioscience

Dartmouth College

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

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关联

3

项与 ABY-029 相关的临床试验

NCT03282461 / Completed早期临床1期IIT

A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Operable Head and Neck Cancer.

The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to detectable signals (defined as signal-to-noise ratio, SNR ≥10, with wide-field iFI) in sampled tissues with an EGFR (epidermal growth factor receptor) pathology score ≥ 1 based on histological staining.
The secondary study objective is to assess ex vivo the specificity of tumor binding in resected specimens by measuring the corresponding molecular uptake and concentrations using histopathology.

开始日期2018-01-24

申办/合作机构

Dartmouth-Hitchcock Medical Center

[+1]

NCT03154411 / Completed早期临床1期IIT

A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Primary Sarcoma.

The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to detectable signals (defined as signal-to-noise ratio, SNR ≥10, with the Odyssey NIR scanner in sampled tissues with an EGFR pathology score ≥ 1 based on histological staining and compare SNR to tissues with an EGFR pathology score < 1).
The secondary study objective is to assess if the spatial patterns of EGFR expression correlate with the tumor targeting of ABY-029 detection by NIR scanner relative to histopathology diagnosis, and other indicators (e.g. proliferation, infiltration, etc.) as the gold standard, and to measure the molecular uptake and concentration of ABY-029 in resected specimens.

开始日期2017-08-30

申办/合作机构

Dartmouth-Hitchcock Medical Center

[+1]

NCT02901925 / Completed早期临床1期IIT

A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Recurrent Glioma

The primary study objective is to determine if microdoses of ABY-029 lead to detectable signals in sampled tissues with an EGFR pathology score ≥ 1 based on histological staining.
The secondary study objective is to assess diagnostic accuracy of ABY-029 detection by iFI and intraoperative probe relative to histopathology diagnosis, and other indicators (e.g. proliferation, infiltration, etc.) as the gold standard, and to measure the molecular uptake and concentration of ABY-029 in resected specimens.

开始日期2017-02-13

申办/合作机构

Dartmouth-Hitchcock Medical Center

[+1]

100 项与 ABY-029 相关的临床结果

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100 项与 ABY-029 相关的转化医学

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100 项与 ABY-029 相关的专利（医药）

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23

项与 ABY-029 相关的文献（医药）

2024-06-01·Annals of Biomedical Engineering

Quantifying Imaging Agent Binding and Dissociation in 3-D Cancer Spheroid Tissue Culture Using Paired-Agent Principles

Article

作者: He, Yusheng ; Brankov, Jovan G ; Tichauer, Kenneth M ; Torres, Veronica C ; Xu, Xiaochun ; Li, Chengyue ; Samkoe, Kimberley S ; Papavasiliou, Georgia ; Rounds, Cody C

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k₃) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k₃ (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

2024-04-01·Molecular Imaging and Biology

Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas

Article

作者: Hoopes, P Jack ; Jarvis, Lesley A ; Werth, Paul M ; Pogue, Brian W ; Samkoe, Kimberley S ; Xu, Xiaochun ; Henderson, Eric R ; Paulsen, Keith D ; Hebert, Kendra A ; Streeter, Samuel S

PURPOSEABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for fluorescence-guided surgery of sarcomas. To date, studies using ABY-029 have occurred in tumors naïve to chemotherapy (CTx) and radiation therapy (RTx), although these neoadjuvant therapies are frequently used for sarcoma treatment in humans. The goal of this study was to evaluate the impact of CTx and RTx on tumor EGFR expression and ABY-029 fluorescence of human soft-tissue sarcoma xenografts in a murine model.PROCEDURESImmunodeficient mice (n = 98) were divided into five sarcoma xenograft groups and three treatment groups - CTx only, RTx only, and CTx followed by RTx, plus controls. Four hours post-injection of ABY-029, animals were sacrificed followed by immediate fluorescence imaging of ex vivo adipose, muscle, nerve, and tumor tissues. Histological hematoxylin and eosin staining confirmed tumor type, and immunohistochemistry staining determined EGFR, cluster of differentiation 31 (CD31), and smooth muscle actin (SMA) expression levels. Correlation analysis (Pearson's correlation coefficients, r) and linear regression (unstandardized coefficient estimates, B) were used to determine statistical relationships in molecular expression and tissue fluorescence between xenografts and treatment groups.RESULTSNeoadjuvant therapies had no broad impact on EGFR expression (|B|≤ 7.0, p ≥ 0.4) or on mean tissue fluorescence (any tissue type, (|B|≤ 2329.0, p ≥ 0.1). Mean tumor fluorescence was significantly related to EGFR expression (r = 0.26, p = 0.01), as expected.CONCLUSIONResults suggest that ABY-029 as an EGFR-targeted, fluorescent probe is not negatively impacted by neoadjuvant soft-tissue sarcoma therapies, although validation in humans is required.

2024-03-01·Biomedical Optics Express

Quantitative pharmacokinetic and biodistribution studies for fluorescent imaging agents

Article

作者: Samkoe, Kimberley S ; Hodge, Sassan ; Rounds, Cody ; Feng, Yichen ; Paulsen, Keith D ; Pannem, Sanjana ; Tichauer, Kenneth M

Pharmacokinetics and biodistribution studies are essential for characterizing fluorescent agents in vivo. However, few simple methods based on fluorescence imaging are available that account for tissue optical properties and sample volume differences. We describe a method for simultaneously quantifying mean fluorescence intensity of whole blood and homogenized tissues in glass capillary tubes for two fluorescent agents, ABY-029 and IRDye 680LT, using wide-field imaging and tissue-specific calibration curves. All calibration curves demonstrated a high degree of linearity with mean R2 = 0.99 ± 0.01 and RMSE = 0.12 ± 0.04. However, differences between linear regressions indicate that tissue-specific calibration curves are required for accurate concentration recovery. The lower limit of quantification (LLOQ) for all samples tested was determined to be < 0.3 nM for ABY-029 and < 0.4 nM for IRDye 680LT.

100 项与 ABY-029 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
头颈部肿瘤	临床2期	美国	Dartmouth College	2018-01-24
软组织肉瘤	临床2期	美国	Dartmouth College	2017-08-30
复发性胶质瘤	临床2期	美国	Dartmouth College	2017-02-13
胶质瘤	临床1期	-	Affibody AB	-
胶质瘤	临床1期	-	Dartmouth College	-
胶质瘤	临床1期	-	Li-Cor Bioscience	-