PRL3-zumab(PRL3-zumab) - 药物靶点：PRL-3_在研适应症：实体瘤，晚期恶性实体瘤，肝细胞癌_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

靶点

PRL-3

作用机制

PRL-3抑制剂(protein tyrosine phosphatase 4A3 inhibitors)

治疗领域

肿瘤消化系统疾病血液及淋巴系统疾病

在研适应症

实体瘤晚期恶性实体瘤肝细胞癌+ [2]

非在研适应症-

原研机构

Intra-ImmuSG Pte Ltd

在研机构

Intra-ImmuSG Pte Ltd

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评-

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关联

4

项与 PRL3-zumab 相关的临床试验

CTR20211180 / Recruiting临床2期

一项针对实体瘤、评估PRL3-Zumab安全性和有效性的开放标签、多中心2期研究

主要目的: 证明PRL3-Zumab在不可切除或转移性实体瘤患者中的疗效

开始日期2021-07-14

申办/合作机构

精鼎医药研究开发（上海）有限公司

[+1]

NCT04452955 / Active, not recruiting临床2期

An Open Label, Multicenter, Safety and Efficacy Phase 2 Study of PRL3-Zumab in Solid Tumors

This is a multi-center, Phase 2, open-label, single dose level study of PRL3-zumab monotherapy in patients with unresectable or metastatic solid tumor.

开始日期2020-12-12

申办/合作机构

Intra-ImmuSG Pte Ltd

[+1]

NCT04118114 / Recruiting临床2期IIT

An Open Label Phase II Study of the Efficacy and Tolerability of PRL3-ZUMAB and Predictive Biomarkers in Advanced Solid Tumours

This is a Phase II, open-label, single dose level study of PRL3-ZUMAB monotherapy in patients with advanced solid tumours that have failed standard therapy. Approximately 30 patients will be recruited with
10 gastric cancers and
10 hepatocellular carcinomas. Patients who have received at least 1 dose of PRL3-ZUMAB will be evaluable for toxicity and efficacy.
PRL3-ZUMAB will be given IV every 2 weeks for up to 12 infusions in the absence of unmanageable toxicities or disease progression. Patients who are benefitting from the treatment may continue on PRL3-ZUMAB beyond 12 infusions with the agreement of the study drug provider.
PRL3-ZUMAB at the RP2D in tumour types enriched for known PRL-3 expression for efficacy and tolerability will be evaluated. There will also be in depth molecular profiling of tissues in patients who have an objective response or prolonged disease stabilization to identify predictive/selection biomarkers as well as evaluation of the oncogenic signaling modulation and immunomodulation by PRL3-ZUMAB and its potential for future combination with other targeted therapies or immunotherapy.

开始日期2019-09-03

申办/合作机构

National Cancer Centre of Singapore Pte Ltd.

[+1]

100 项与 PRL3-zumab 相关的临床结果

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100 项与 PRL3-zumab 相关的转化医学

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100 项与 PRL3-zumab 相关的专利（医药）

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9

项与 PRL3-zumab 相关的文献（医药）

2023-09-01·Molecular Therapy - Oncolytics

Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody

Article

作者: Seng, Michaela Su-Fern ; Merchant, Khurshid ; Chia, Pei Ling ; Loh, Amos Hong Pheng ; Chang, Kenneth Tou En ; Gupta, Abhishek ; Kuan, Kelvin Kam Yew ; Yon, Hui Yi ; Iyer, Prasad ; Tan, Sheng Hui ; Thura, Min ; Cheng, Mathew Hern Wang ; Zeng, Qi ; Mahadev, Arjandas ; Soh, Shui Yen ; Ang, Koon Hwee ; Chen, Yong ; Ng, Matthew Chau Hsien

Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets. PRL3-zumab, a first-in-class humanized antibody, was administered in a dose escalation schedule in a first-in-child clinical trial to study toxicity, pharmacokinetics, and clinical outcomes. Among 64 pediatric tumors, PRL3 was most frequently expressed in neuroblastoma (100%), rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcomas (71%), and renal sarcomas (60%) but absent in paired normal tissues. PRL3 was expressed in 75% of relapsed tumors and associated with shorter median event-free survival. Microarray profiling of PRL3-positive tumors showed elevation of angiogenin, TIMP1 and TIMP2, and GPCR-MAPK signaling proteins that commonly interacted with PRL3. The first use of PRL3-zumab in a pediatric patient saw no adverse events. A 28.6% reduction in maximum target lesion diameter was achieved when PRL3-zumab was administered concurrently with hypofractionated radiation. These findings support wider exploration of PRL3 expression in embryonal and mesenchymal tumors and further clinical application of PRL3-zumab in pediatric patients.

2023-05-01·Targeted oncology

A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies.

Article

作者: Zeng, Qi ; Thura, Min ; Al-Aidaroos, Abdul Qader ; Heong, Valerie ; Lee, Soo-Chin ; Ng, Chin Hin ; Tan, Joshua T C ; Yang, Song ; Goh, Boon-Cher ; Chng, Wee Joo ; Soo, Ross ; Ooi, Melissa ; Tan, David S P ; Yong, Wei-Peng ; Lim, Joline S J ; Wong, Andrea ; Chee, Cheng E ; Sundar, Raghav

BACKGROUNDPhosphatase of regenerating liver-3 (PRL-3) is involved in cellular processes driving metastasis, cell proliferation, invasion, motility and survival. It has been shown to be upregulated and overexpressed in cancer tissue, in contrast to low or no expression in most normal tissue. PRL3-zumab is a first-in-class humanized antibody that specifically binds to PRL-3 oncotarget with high affinity and has been shown to reduce tumor growth and increase survival.OBJECTIVEIn the study, we aimed to determine the safety and efficacy of PRL3-zumab in patients with advanced solid tumors and hematological malignancies.METHODSWe conducted a phase I, first-in-human study in advanced solid tumors and hematological malignancies to investigate the safety, tolerability and efficacy of PRL3-zumab. Response rates were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) for solid tumors. For acute myeloid leukemia (AML) patients, bone marrow response criteria based on the European Leukaemia Network (ELN) 2017 guidelines for AML were used. We also explored the pharmacokinetics and pharmacodynamic relationships of PRL3-zumab in patients. This study was registered with ClinicalTrials.gov: NCT03191682.RESULTSIn the dose-escalation cohort, 11 patients with advanced solid tumors were enrolled into the study. An additional 12 patients with solid tumors and four patients with AML were enrolled in the dose-expansion cohort. Maximum tolerability was not achieved in this study, as there were no dose-limiting toxicities. Potential treatment-emergent adverse events were grade 1 increased stoma output and fatigue and grade 2 vomiting. Best response observed was stable disease in three solid-tumor patients (11.1%). The pharmacokinetics of PRL3-zumab were dose proportional, consistent with an IgG type monoclonal antibody.CONCLUSIONSPRL3-zumab, a first-in-class humanized antibody, was safe and tolerable in solid tumors and hematological malignancies.

2023-01-01·Theranostics

PRL3 as a therapeutic target for novel cancer immunotherapy in multiple cancer types.

Review

作者: Ang, Koon Hwee ; Chia, Pei Ling ; Thura, Min ; Zeng, Qi

A review.Phosphatase of Regenerating Liver-3 (PRL3) was discovered in 1998 and was subsequently found to be correlated with cancer progression and metastasis in 2001.Extensive research in the past two decades has produced significant findings on PRL3-mediated cancer signaling and functions, as well as its clin. relevance in diverse types of cancer.PRL3 has been established to play a role in many cancer-related functions, including but not limited to metastasis, proliferation, and angiogenesis.Importantly, the tumor-specific expression of PRL3 protein in multiple cancer types has made it an attractive therapeutic target.Much effort has been made in developing PRL3-targeted therapy with small chem. inhibitors against intracellular PRL3, and notably, the development of PRL3-zumab as a novel cancer immunotherapy against PRL3.In this review, we summarize the current understanding of the role of PRL3 in cancer-related cellular functions, its prognostic value, as well as perspectives on PRL3 as a target for unconventional immunotherapy in the clinic with PRL3-zumab.

100 项与 PRL3-zumab 相关的药物交易

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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
实体瘤	临床2期	中国	Intra-ImmuSG Pte Ltd	2021-07-14
晚期恶性实体瘤	临床2期	新加坡	Intra-ImmuSG Pte Ltd	2019-09-03
肝细胞癌	临床2期	新加坡	Intra-ImmuSG Pte Ltd	2019-09-03
胃癌	临床2期	新加坡	Intra-ImmuSG Pte Ltd	2019-09-03
急性髓性白血病	临床1期	新加坡	Intra-ImmuSG Pte Ltd	-
血液肿瘤	临床前	新加坡	Intra-ImmuSG Pte Ltd	2017-02-20