Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center)(Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center))

概要

基本信息

药物类型

抗体偶联核素、诊断用放射药物

别名

Omburtamab I-124

+ [1]

靶点

CD276

作用机制

CD276抑制剂(CD276抗原抑制剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

肿瘤神经系统疾病其他疾病

在研适应症-

非在研适应症

脑干胶质瘤弥漫内生性脑桥神经胶质瘤

原研机构

Y-mAbs Therapeutics, Inc.

在研机构-

非在研机构

Memorial Sloan Kettering Cancer Center

Y-mAbs Therapeutics, Inc.

最高研发阶段无进展临床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/序列

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Sequence Code 319910812L

Sequence Code 432498306H

关联

2

项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 相关的临床试验

NCT01502917

/ Completed临床1期

A Phase I Study of Convection-Enhanced Delivery of 124I-Omburtamab for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

The purpose of this study is to test the safety of a new method to treat Diffuse Intrinsic Pontine Glioma (DIPG). The researchers will use "convection-enhanced delivery" (CED) to deliver an agent called 124I-omburtamab. CED is performed during surgery. The study agent is infused through a small tube placed into the tumor in the brain. Many studies have shown this can safely be done in animals but this study is the first time 124I-omburtamab will be given by CED in humans. This will be one of the first times that CED has been performed in the brain stem.
Omburtamab is something called an antibody. Antibodies are made by the body to fight infections and sometimes cancer. The antibody omburtamab is produced by mice and can attack many kinds of tumors. A radioactive substance, 124I-omburtamab, is attached to omburtamab. 124I-omburtamab sticks to parts of tumor cells and can cause the tumor cells to die from radiation. Studies have also been done on humans using 124I-omburtamab to treat other kinds of cancer. Our studies of some DPG and related tumors suggest that omburtamab will bind to the tumor, but the investigators don't know that for sure.
In this study, the researchers want to find out how safe 124I-omburtamab given by CED is at different dose levels. They will look to see what effects (both good and bad) it has on the patient. The dose of 124I-omburtamab will increase for each new group of patients. The procedure has already been safely performed with lower doses and infusion volumes in a number of patients here at MSKCC. The amount they get will depend on when they enter the study. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some more patients may be treated with a lower dose to make sure that dose is safe.

开始日期2011-12-01

申办/合作机构

Y-mAbs Therapeutics, Inc.

[+1]

NCT00582608

/ TerminatedN/AIIT

Tumor Detection Using Iodine-131-Labeled Monoclonal Antibody 8H9

The purpose of this study is to find out whether the monoclonal antibody 8H9 is useful in finding tumors in your body. Antibodies are protein found naturally in blood. They can fasten themselves to bacteria and viruses. They can stimulate white cells and blood proteins to kill tumors. The antibody 8H9 was made from mouse white cells. The white cells that secrete this antibody have been made to live for ever. They manufacture large amounts of 8H9 for patient use. Although other monoclonal antibodies have been safely tested in people, the antibody 8H9 has never been given to a human patient.

开始日期2001-10-01

申办/合作机构

Memorial Sloan Kettering Cancer Center

100 项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 相关的临床结果

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100 项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 相关的转化医学

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100 项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 相关的专利（医药）

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6

项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 相关的文献（医药）

2024-09-01·Journal of Nuclear Medicine

Theranostic Intratumoral Convection-Enhanced Delivery of¹²⁴I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry

Article

作者: Vietri, Scott M ; Lyashchenko, Serge ; Donzelli, Maria ; Serencsits, Brian ; Dunkel, Ira J ; Horan, Christopher ; Zanzonico, Pat B ; Kramer, Kim ; Pandit-Taskar, Neeta ; Souweidane, Mark M ; Grkovski, Milan ; Prasad, Kavya

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using ¹²⁴I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of ¹²⁴I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of ¹²⁴I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean ¹²⁴I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of ¹²⁴I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of ¹²⁴I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.

2023-06-01·Journal of Nuclear Medicine

Radioimmunoscintigraphy and Pretreatment Dosimetry of¹³¹I-Omburtamab for Planning Treatment of Leptomeningeal Disease

Article

作者: Zanzonico, Pat B ; Pandit-Taskar, Neeta ; Humm, John L ; Pentlow, Keith S ; Kramer, Kim ; Grkovski, Milan ; Modak, Shakeel

Radiolabeled antibody treatment with ¹³¹I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment ¹³¹I-omburtamab imaging and dosimetric analysis in patients before therapy. Methods: Whole-body planar images were acquired 3 ± 1, 23 ± 2, and 47 ± 2 h after intracranioventricular administration of 75 ± 5 MBq of ¹³¹I-omburtamab via an Ommaya reservoir. Multiple blood samples were also obtained for kinetic analysis. Separate regions of interest (ROIs) were manually drawn to include the lateral ventricles, entire spinal canal CSF space, and over the whole body. Count data in the ROIs were corrected for background and physical decay, converted to activity, and subsequently fitted to an exponential clearance function. The radiation absorbed dose was estimated to the CSF, separately to the spinal column and ventricles, and to the whole body and blood. Biodistribution of the injected radiolabeled antibody was assessed for all patients. Results: Ninety-five patients were included in the analysis. Biodistribution showed prompt localization in the ventricles and spinal CSF space with low systemic distribution, noted primarily as hepatic, renal, and bladder activity after the first day. Using ROI analysis, the effective half-lives were 13 ± 11 h (range, 5-75 h) for CSF in the spinal column, 8 ± 3 h (range, 3-17 h) for ventricles, and 41 ± 11 (range, 23-81 h) for the whole body. Mean absorbed doses were 0.63 ± 0.38 cGy/MBq (range, 0.24-2.25 cGy/MBq) for CSF in the spinal column, 1.03 ± 0.69 cGy/MBq (range, 0.27-5.15 cGy/MBq) for the ventricular CSF, and 0.45 ± 0.32 mGy/MBq (range, 0.05-1.43 mGy/MBq) for the whole body. Conclusion: Pretherapeutic imaging with ¹³¹I-omburtamab allows assessment of biodistribution and dosimetry before the administration of therapeutic activity. Absorbed doses to the CSF compartments and whole body derived from the widely applicable serial ¹³¹I-omburtamab planar images had acceptable agreement with previously reported data determined from serial ¹²⁴I-omburtamab PET scans.

2022-07-01·Journal of Nuclear Medicine1区 · 医学

Biodistribution and Radiation Dosimetry of Intraperitoneally Administered ¹²⁴I-Omburtamab in Patients with Desmoplastic Small Round Cell Tumors

1区 · 医学

Article

作者: Pandit-Taskar, Neeta ; Carrasquillo, Jorge A ; Grkovski, Milan ; Humm, John L ; Zanzonico, Pat B ; Larson, Steven M ; Modak, Shakeel

The aim of this study was to assess the pharmacokinetics, biodistribution, and radiation dosimetry of ¹²⁴I-omburtamab administered intraperitoneally in patients with desmoplastic small round cell tumor. Methods: Eligible patients diagnosed with desmoplastic small round cell tumor with peritoneal involvement were enrolled in a phase I trial of intraperitoneal radioimmunotherapy with ¹³¹I-omburtamab. After thyroid blockade and before radioimmunotherapy, patients received approximately 74 MBq of ¹²⁴I-omburtamab intraperitoneally. Five serial PET/CT scans were obtained up to 144 h after injection. Multiple blood samples were obtained up to 120 h after injection. Organ-absorbed doses were calculated with OLINDA/EXM. Results: Thirty-one patients were studied. Blood pharmacokinetics exhibited a biphasic pattern consisting of an initial rising phase with a median half-time (±SD) of 23 ± 15 h and a subsequent falling phase with a median half-time of 56 ± 34 h. Peritoneal distribution was heterogeneous and diffuse in most patients. Self-dose to the peritoneal cavity was 0.58 ± 0.19 mGy/MBq. Systemic distribution and activity in major organs were low. The median absorbed doses were 0.72 ± 0.23 mGy/MBq for liver, 0.48 ± 0.17 mGy/MBq for spleen, and 0.57 ± 0.12 mGy/MBq for kidneys. The mean effective dose was 0.31 ± 0.10 mSv/MBq. Whole-body and peritoneal cavity biologic half-times were 45 ± 9 and 24 ± 5 h, respectively. Conclusion: PET/CT imaging with intraperitoneally administered ¹²⁴I-omburtamab enables assessment of intraperitoneal distribution and estimation of absorbed dose to peritoneal space and normal organs before therapy.

100 项与 Monoclonal antibody 8H9 I-124(Memorial Sloan Kettering Cancer Center) 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
脑干胶质瘤	临床1期	美国	Y-mAbs Therapeutics, Inc.	2011-12-01
弥漫内生性脑桥神经胶质瘤	临床1期	美国	Memorial Sloan Kettering Cancer Center	2011-12-01
弥漫内生性脑桥神经胶质瘤	临床1期	美国	Y-mAbs Therapeutics, Inc.	2011-12-01
脑干胶质瘤	药物发现	美国	Memorial Sloan Kettering Cancer Center	2011-12-01

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临床结果

适应症

分期

评价

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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


NCT01502917 (MSKCC 11-011, ASCO 12021 \| ASCO 22021) 人工标引	临床1期	弥漫内生性脑桥神经胶质瘤	46	124I-omburtamab	(膚顧積選構淵鹹選鹽顧) = Eight patients have reported transient AEs of grade 3 considered related to 124I-omburtamab. The acute grade 3 AEs were generally indicative of nervous system effects due to volume intolerance or radiation injury, and included hemiparesis (n = 3), dysarthria (n = 3), ataxia (n = 3), dysphagia (n = 2), muscular weakness (n = 2) and gait disturbance (n = 1) 積顧夢衊獵選壓醖壓鬱 (夢衊醖簾範廠鬱廠膚築 )	积极	2021-05-28
NCT01502917 (ASCO2019)	临床1期	弥漫内生性脑桥神经胶质瘤	37	<sup>124</sup>I-8H9 radio-labeled monoclonal antibody	(築鹽繭築艱醖蓋遞糧網) = Among adverse events that were at least possibly related to the treatment, there were no grade 4 or 5 events, and only 4 reversible grade 3 events in 4 patients (2 hemiparesis, 1 skin infection and 1 anxiety) 膚齋襯糧鹹衊範餘觸鏇 (製製鏇夢糧範壓鏇糧獵 )	积极	2019-05-26
NCT01502917 (ASCO2017)	临床1期	弥漫内生性脑桥神经胶质瘤	25	<sup>124</sup>I-8H9 radio-labeled monoclonal antibody	衊網觸鹽顧齋網製網觸(醖願願選鑰窪鹹鬱糧壓) = 鬱遞積製餘淵簾壓願獵鑰蓋構構艱鬱鏇齋醖築 (艱觸廠襯繭鏇網選鹽築 ) 更多	积极	2017-05-30