Yttrium 90-radiolabelled OTSA 101(Yttrium 90-radiolabelled OTSA 101) - 药物靶点：FZD10_在研适应症：肉瘤_专利_临床

概要

基本信息

药物类型

抗体偶联核素、治疗用放射药物

别名

Yttrium 90-radiolabeled tabituximab、tabituximab barzuxetan

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靶点

FZD10

作用机制

FZD10拮抗剂(卷曲蛋白受体10拮抗剂)、电离辐射发射源

治疗领域

肿瘤

在研适应症

肉瘤

非在研适应症

难治性滑膜肉瘤复发性滑膜肉瘤

原研机构

OncoTherapy Science, Inc.

在研机构

Centre Léon Bérard Lyon et Rhône-Alpes

非在研机构

OncoTherapy Science, Inc.

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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序列信息

Sequence Code 616718396L

来源: *****

Sequence Code 616718390H

来源: *****

关联

2

项与 Yttrium 90-radiolabelled OTSA 101 相关的临床试验

NCT04176016 / Terminated临床1期

Safety Study of Radiolabeled (111In or 90Y) OTSA101-DTPA, an Anti-Frizzled Homolog 10 (FZD10) Monoclonal Antibody, to Evaluate Safety and Pharmacokinetics in Patients With Relapsed or Refractory Synovial Sarcoma

The purpose of this study is to evaluate safety and pharmacokinetics as well as the biodistribution of OTSA101-DTPA-111In and to evaluate the safety of intravenous administration of OTSA101-DTPA-90Y.

开始日期2020-01-10

申办/合作机构

OncoTherapy Science, Inc.

NCT01469975 / Terminated临床1期IIT

First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10 (FZD10) in Patients With Relapsed or Refractory Non Resectable Synovial Sarcomas

Advanced synovial sarcoma represents an unmet medical need. The gene encoding frizzled homologue 10 (FZD10), a 7-transmenbrane receptor, member of the Wnt signalling receptor family, is overexpressed in SS and is undetectable in normal human tissues except placenta.
OncoTherapy Science Inc. has developed a chimeric humanized monoclonal antibody (mAb) against FZD10, named OTSA101. Non-radiolabeled OTSA101 antibody has only weak antagonistic activity on SS cell growth. However, Yttrium 90-radiolabeled OTSA101 (OTSA101-DTPA-90Y) showed significant antitumor activity following a single intravenous injection in mouse xenograft model.
This first in man clinical trial (Phase I) in relapsing SS patients resistant to Doxorubicin and ifosfamide will be divided in 2 parts.
In Part 1 (imaging part using OTSA101 radiolabelled with Indium 111 [111In]), the biodistribution and tumor uptake of OTSA101-DTPA-111In will be followed using 111In as radiotracer.
In Part 2 (therapeutic part with OTSA101 radiolabelled with Yttrium 90 [90Y]), the safety and PK profiles of OTSA101-DTPA-90Y will be determined and preliminary efficacy data will be collected.
This first in Man study should allow defining the optimal recommended dose of OTSA101-DTPA-90Y.
Patients will be followed during 1 year.

开始日期2011-12-01

申办/合作机构

Centre Léon Bérard Lyon et Rhône-Alpes

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100 项与 Yttrium 90-radiolabelled OTSA 101 相关的临床结果

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100 项与 Yttrium 90-radiolabelled OTSA 101 相关的转化医学

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100 项与 Yttrium 90-radiolabelled OTSA 101 相关的专利（医药）

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84

项与 Yttrium 90-radiolabelled OTSA 101 相关的文献（医药）

2023-12-01·Cancer Science

Head‐to‐head comparison of three chelates reveals DOTAGA promising for ²²⁵Ac labeling of anti‐FZD10 antibody OTSA101

Article

作者: Nagayama, Satoshi ; Higashi, Tatsuya ; Katagiri, Toyomasa ; Harada, Yosuke ; Nakamura, Yusuke ; Tsuji, Atsushi B ; Sugyo, Aya ; Sudo, Hitomi

AbstractTo select the most suitable chelate for 225Ac radiolabeling of the anti‐FZD10 antibody OTSA101, we directly compared three chelates: S‐2‐(4‐isothiocyanatobenzyl)‐1,4,7,10‐tetraazacyclododecane tetraacetic acid (p‐SCN‐Bn‐DOTA), 2,2′,2″‐(10‐(1‐carboxy‐4‐((4‐isothiocyanatobenzyl)amino)‐4‐oxobutyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyl) triacetic acid (p‐SCN‐Bn‐DOTAGA), and 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid mono‐N‐hydroxysuccinimide ester (DO3A‐NHS‐ester). We evaluated the binding affinity of the chelate‐conjugated OTSA101 antibodies, as well as the labeling efficiency and stability in murine serum of 225Ac‐labeled OTSA101 as in vitro properties. The biodistribution, intratumoral distribution, absorbed doses, and therapeutic effects of the chelate‐conjugated OTSA101 antibodies were assessed in the synovial sarcoma mouse model SYO‐1. Of the three conjugates, DOTAGA conjugation had the smallest impact on the binding affinity (p < 0.01). The labeling efficiencies of DOTAGA‐OTSA101 and DO3A‐OTSA101 were 1.8‐fold higher than that of DOTA‐OTSA101 (p < 0.01). The stabilities were similar between 225Ac‐labeled DOTA‐OTSA101, DOTAGA‐OTSA101, and DO3A‐OTSA101in serum at 37 and 4°C. The dosimetric analysis based on the biodistribution revealed significantly higher tumor‐absorbed doses by 225Ac‐labeled DOTA‐OTSA101 and DOTAGA‐OTSA101 compared with 225Ac‐DO3A‐OTSA101 (p < 0.05). 225Ac‐DOTAGA‐OTSA101 exhibited the highest tumor‐to‐bone marrow ratio, with bone marrow being the dose‐limiting tissue. The therapeutic and adverse effects were not significantly different between the three conjugates. Our findings indicate that among the three evaluated chelates, DOTAGA appears to be the most promising chelate to produce 225Ac‐labeled OTSA101 with high binding affinity and high radiochemical yields while providing high absorbed doses to tumors and limited absorbed doses to bone marrow.

2023-04-26·Journal of personalized medicine

Targeted Treatment of Soft-Tissue Sarcoma.

Review

作者: Riskjell, Anne Iren ; Aggerholm-Pedersen, Ninna ; Sandfeld-Paulsen, Birgitte ; Mäkinen, Vivi-Nelli

Background: Soft-tissue sarcoma (STS) is a heterogeneous group of sarcomas with a low incidence. The treatment of advanced disease is poor, and mortality is high. We aimed to generate an overview of the clinical experiences with targeted treatments based on a pre-specified target in patients with STS. Methods: A systematic literature search was conducted in PubMed and Embase databases. The programs ENDNOTE and COVIDENCE were used for data management. The literature was screened to assess the article's eligibility for inclusion. Results: Twenty-eight targeted agents were used to treat 80 patients with advanced STS and a known pre-specified genetic alteration. MDM2 inhibitors were the most-studied drug (n = 19), followed by crizotinib (n = 9), ceritinib (n = 8), and ⁹⁰Y-OTSA (n = 8). All patients treated with the MDM2 inhibitor achieved a treatment response of stable disease (SD) or better with a treatment duration of 4 to 83 months. For the remaining drugs, a more mixed response was observed. The evidence is low because most studies were case reports or cohort studies, where only a few STS patients were included. Conclusions: Many targeted agents can precisely target specific genetic alterations in advanced STS. The MDM2 inhibitor has shown promising results.

2022-08-01·Journal of Applied Clinical Medical Physics

Comparison of Eclipse Smart Segmentation and MIM Atlas Segment for liver delineation for yttrium‐90 selective internal radiation therapy

Article

作者: Li, Jun ; Anne, Rani

AbstractPurposeThe aim was to compare Smart Segmentation of Eclipse treatment planning system and Atlas Segment of MIM software for liver delineation for resin yttrium‐90 (Y‐90) procedures.Materials and methodsCT images of 20 patients treated with resin Y‐90 selective internal radiation therapy (SIRT) were tested. Liver contours generated with Smart Segmentation and Atlas Segment were compared with physician manually delineated contours. Dice similarity coefficient (DSC), mean distance to agreement (MDA), and ratio of volume (RV) were calculated. The contours were evaluated with activity calculations and ratio of activity (RA) was calculated.ResultsMean DSCs were 0.77 and 0.83, MDAs were 0.88 and 0.71 cm, mean RVs were 0.95 and 1.02, and mean RAs were 1.00 and 1.00, for Eclipse and MIM results, respectively.ConclusionMIM outperformed Eclipse in both DSC and MDA, whereas the differences in liver volumes and calculated activities were statistically insignificant between the Eclipse and MIM results. Both auto‐segmentation tools can be used to generate initial liver contours for resin Y‐90 SIRT, which need to be reviewed and edited by physicians.

100 项与 Yttrium 90-radiolabelled OTSA 101 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
难治性滑膜肉瘤	临床2期	日本	OncoTherapy Science, Inc.	2020-01-10
肉瘤	临床1期	-	Centre Léon Bérard Lyon et Rhône-Alpes	-

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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


NCT01469975 (Pubmed \| BMC Cancer) 人工标引	临床1期	滑膜肉瘤	-	OTSA-101	(鏇鏇糧夢廠餘齋積壓鑰) = reversible hematological disorders 遞淵遞夢襯餘餘鏇網繭 (鏇鑰淵蓋積襯鹽鏇醖糧 )	积极	2018-06-08