Firtecan pegol(Firtecan pegol) - 药物靶点：HIF-1α x Top I_在研适应症：转移性乳腺癌_专利_临床

概要

基本信息

药物类型

聚合物

别名

Firtecan pegol (USAN/INN)、BEL-0222、EZN-2208

+ [3]

靶点

HIF-1α x Top I

作用方式

抑制剂

作用机制

HIF-1α抑制剂(缺氧诱导因子-1α抑制剂)、TOP1抑制剂(DNA拓扑异构酶I抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症

转移性乳腺癌

非在研适应症

晚期恶性实体瘤淋巴瘤转移性结直肠癌+ [1]

原研机构

Enzon Pharmaceuticals, Inc.

在研机构

浙江海正药业股份有限公司

非在研机构

Enzon Pharmaceuticals, Inc.

权益机构

浙江海正药业股份有限公司Belrose Pharma, Inc.

Enzon Pharmaceuticals, 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)临床1期

特殊审评孤儿药 (美国)

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结构/序列

分子式C118H122N12O37

InChIKeyCXWRXYDTWCBSJF-UHFFFAOYSA-N

CAS号946062-05-1

关联

7

项与 Firtecan pegol 相关的临床试验

NCT01251926

/ Completed临床1期IIT

Pilot Study of Weekly EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

Background:
- The anticancer drug bevacizumab works by reducing the formation of new blood vessels in tumors, which can slow or stop the growth of cancer cells and supporting blood vessels. The experimental drug EZN-2208 works by limiting how well cancer cells can divide. Drugs similar to EZN-2208 also work by turning off the production of the HIF protein, which otherwise can help cancer cells to grow even when blood supply is limited. Researchers are interested in determining if EZN-2208 turns off HIF in patient tumors, and whether combining it with bevacizumab is an effective treatment for cancers that have not responded to standard treatment.
Objectives:
- To assess the safety and effectiveness of the combination of EZN-2208 and bevacizumab for solid tumors that have not responded to standard treatment.
Eligibility:
- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment.
Design:
* Participants will be screened with a full physical examination and medical history, blood and urine samples, and tumor imaging studies.
* Participants will receive EZN-2208 and bevacizumab intravenously on an outpatient basis in 4-week cycles (with the exception of the first cycle, which will be 5 weeks).
* Cycle 1: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab 1 week before EZN-2208 (day - 7) and then 3 weeks later (day 15).
* Subsequent cycles: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab every 2 weeks (days 1 and 15).
* Participants will have clinic visits with physical examinations and blood tests in the first 3 weeks of each cycle. Clinic visits may also include tumor imaging studies and tumor biopsies as directed by the study researchers.
* Participants will continue to take the study drugs for as long as the tumor shrinks or does not grow, and as long as they do not experience intolerable or unsafe side effects from the drugs.

开始日期2010-11-15

申办/合作机构

National Cancer Institute

NCT01295697

/ Terminated临床1/2期

A Phase 1/2 Study of EZN-2208 in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

The goal of this clinical research study is to find the highest tolerable dose of EZN-2208 that can be given to pediatric patients with Relapsed or Refractory Solid Tumors. The safety of the study drug and its effect on the disease will also be studied.

开始日期2010-02-01

申办/合作机构

Enzon Pharmaceuticals, Inc.

NCT01036113

/ Terminated临床2期

A Phase 2, Open-Label Study of EZN-2208 (PEG-SN38) in Patients With Previously Treated Metastatic Breast Cancer (MBC)

This is a Phase 2, multicenter, open-label, noncomparative study to evaluate safety,efficacy and of single-agent EZN 2208 administered in patients with previously treated MBC.
After discontinuation of study treatment, patients will receive care as considered appropriate by the investigator. Patients will continue to be followed for disease progression, subsequent anticancer therapy, and survival.

开始日期2009-11-01

申办/合作机构

Enzon Pharmaceuticals, Inc.

100 项与 Firtecan pegol 相关的临床结果

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100 项与 Firtecan pegol 相关的转化医学

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100 项与 Firtecan pegol 相关的专利（医药）

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11

项与 Firtecan pegol 相关的文献（医药）

2020-05-01·Open biology2区 · 生物学

EZN-2208 treatment suppresses chronic lymphocytic leukaemia by interfering with environmental protection and increases response to fludarabine

2区 · 生物学

ArticleOA

作者: Bongiovanni, Lucia ; Bernardi, Rosa ; Valsecchi, Roberta ; Scarfò, Lydia ; Ghia, Paolo ; Magliulo, Daniela ; Ponzoni, Maurilio ; Coltella, Nadia

The transcription factor HIF-1α is overexpressed in chronic lymphocytic leukaemia (CLL), where it promotes leukaemia progression by favouring the interaction of leukaemic cells with protective tissue microenvironments. Here, we tested the hypothesis that a pharmacological compound previously shown to inhibit HIF-1α may act as a chemosensitizer by interrupting protective microenvironmental interactions and exposing CLL cells to fludarabine-induced cytotoxicity. We found that the camptothecin-11 analogue EZN-2208 sensitizes CLL cells to fludarabine-induced apoptosis in cytoprotective in vitro cultures; in vivo EZN-2208 improves fludarabine responses, especially in early phases of leukaemia expansion, and exerts significant anti-leukaemia activity, thus suggesting that this or similar compounds may be considered as effective CLL therapeutic approaches.

2014-10-01·Pediatric blood & cancer3区 · 医学

Phase 1 evaluation of EZN-2208, a polyethylene glycol conjugate of SN38, in children adolescents and young adults with relapsed or refractory solid tumors

3区 · 医学

Article

作者: Robin E. Norris ; Rochelle Bagatell ; Elizabeth Fox ; Noah Berkowitz ; Aby Buchbinder ; Lia Gore ; Jodi A. Muscal ; Suzanne Shusterman ; Margaret E. Macy

BACKGROUND:

EZN-2208 is a water-soluble PEGylated conjugate of the topoisomerase inhibitor SN38, the active metabolite of irinotecan. Compared to irinotecan, EZN-2208 has a prolonged half-life permitting extended exposure to SN38. EZN-2208 has demonstrated clinical tolerability and antitumor activity in adults with advanced solid tumors. This Phase 1 study evaluated the safety, pharmacokinetics, and preliminary antitumor activity of EZN-2208 in children with relapsed or refractory solid tumors.

PROCEDURE:

EZN-2208 was administered as a 1-hour intravenous infusion once every 21 days at five dose levels (12-30 mg/m(2) ). Filgrastim or pegfilgrastim was administered 24-48 hours after treatment with EZN-2208. The rolling-six design was used for dose determination.

RESULTS:

Thirty eligible patients (15 females; median [range] age 11.5 years [2-21 years]) were treated with EZN-2208. Dose-limiting diarrhea occurred in one patient receiving 16 mg/m(2) and dose-limiting dehydration was seen in one patient receiving 24 mg/m(2) . At dose levels above 16 mg/m(2) , Grade ≥3 myelosuppression was demonstrated in the majority of patients. Additional adverse events included nausea, vomiting, and fatigue. The maximum tolerated dose was identified as 24 mg/m(2) due to dose-limiting thrombocytopenia in two patients receiving 30 mg/m(2) . Two of nine patients with neuroblastoma who were evaluable for response had partial responses. Five patients (four with neuroblastoma) remained on study for ≥8 cycles.

CONCLUSIONS:

EZN-2208 was generally well-tolerated and was associated with clinical benefit in patients with neuroblastoma.

2014-04-01·Investigational new drugs3区 · 医学

Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors

3区 · 医学

Article

作者: Turkbey, Baris ; Melillo, Giovanni ; Rapisarda, Annamaria ; Steinberg, Seth M. ; Kinders, Robert J. ; Park, Sook Ryun ; Fer, Nicole ; Chen, Alice ; Choyke, Peter ; Doroshow, James H. ; Kummar, Shivaani ; Jeong, Woondong

BACKGROUND:

Anti-angiogenic therapies such as bevacizumab upregulate hypoxia-inducible factor-1α (HIF-1α), a possible mechanism of drug resistance. Camptothecin analogues, including SN-38, have been shown to reduce the expression and transcriptional activity of HIF-1α in preclinical models. We hypothesized that co-administration of pegylated SN-38 (EZN-2208) may offset the induction of HIF-1α following bevacizumab treatment, resulting in synergistic antitumor effects.

PATIENTS AND METHODS:

Patients with refractory solid tumors were enrolled. Objectives were to evaluate the modulation of HIF-1α protein and target genes in tumor biopsies following administration of the combination of EZN-2208 administered weekly × 3 (days 1, 8, 15) and bevacizumab administered every 2 weeks, in 28-day cycles, and to establish the safety and tolerability of the combination. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were obtained following bevacizumab alone (before EZN-2208) and after administration of both study drugs.

RESULTS:

Twelve patients were enrolled; ten were evaluable for response. Prolonged stable disease was observed in 2 patients, one with HCC (16 cycles) and another with desmoplastic round cell tumor (7 cycles). Reduction in HIF-1α protein levels in tumor biopsies compared to baseline was observed in 5 of 7 patients. Quantitative analysis of DCE-MRI from 2 patients revealed changes in K(trans) and k(ep). The study closed prematurely as further clinical development of EZN-2208 was suspended by the pharmaceutical sponsor.

CONCLUSION:

Preliminary proof-of-concept for modulation of HIF-1α protein in tumor biopsies following administration of EZN-2208 was observed. Two of 10 patients had prolonged disease stabilization following treatment with the EZN-2208 and bevacizumab combination.

100 项与 Firtecan pegol 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10464	-	-	DB14953

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
复发性实体肿瘤	临床2期	美国	Enzon Pharmaceuticals, Inc.	2010-02-01
转移性乳腺癌	临床2期	美国	Enzon Pharmaceuticals, Inc.	2009-11-01
转移性结直肠癌	临床2期	美国	Enzon Pharmaceuticals, Inc.	2009-06-01
转移性结直肠癌	临床2期	加拿大	Enzon Pharmaceuticals, Inc.	2009-06-01
转移性结直肠癌	临床2期	以色列	Enzon Pharmaceuticals, Inc.	2009-06-01
转移性结直肠癌	临床2期	荷兰	Enzon Pharmaceuticals, Inc.	2009-06-01
转移性结直肠癌	临床2期	英国	Enzon Pharmaceuticals, Inc.	2009-06-01
晚期恶性实体瘤	临床1期	美国	Enzon Pharmaceuticals, Inc.	2007-05-01
淋巴瘤	临床1期	美国	Enzon Pharmaceuticals, Inc.	2007-05-01

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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


ASCO2012	临床2期	转移性乳腺癌辅助	164	EZN-2208 9 mg/m2	製膚齋膚蓋鏇積鏇齋衊(淵蓋願鬱憲製鹹膚壓製) = 糧糧齋糧壓鏇餘襯膚憲鹹鏇廠築衊積齋壓艱糧 (獵製積鏇築糧願製襯願 ) 更多	-	2012-05-20