Delving into the Latest Updates on Firtecan pegol with Synapse

Overview

Basic Info

Drug Type

Polymer

Synonyms

Firtecan pegol (USAN/INN)

+ [3]

Target

HIF-1α x Top I

Mechanism

HIF-1α inhibitors(Hypoxia-inducible factor 1 alpha inhibitors), TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Metastatic breast cancer

Inactive Indication

Advanced Malignant Solid NeoplasmLymphomaMetastatic Colorectal Carcinoma+ [1]

Originator Organization

Enzon Pharmaceuticals, Inc.

Active Organization

Zhejiang Hisun Pharmaceutical Co., Ltd.

Inactive Organization

Enzon Pharmaceuticals, Inc.

Drug Highest PhasePhase 1

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC118H122N12O37

InChIKeyCXWRXYDTWCBSJF-UHFFFAOYSA-N

CAS Registry946062-05-1

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.

Start Date15 Nov 2010

Sponsor / Collaborator

National Cancer Institute

NCT01295697

/ TerminatedPhase 1/2

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.

Start Date01 Feb 2010

Sponsor / Collaborator

Enzon Pharmaceuticals, Inc.

NCT01036113

/ TerminatedPhase 2

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.

Start Date01 Nov 2009

Sponsor / Collaborator

Enzon Pharmaceuticals, Inc.

100 Clinical Results associated with Firtecan pegol

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100 Translational Medicine associated with Firtecan pegol

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100 Patents (Medical) associated with Firtecan pegol

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14

Literatures (Medical) associated with Firtecan pegol

01 May 2020·Open BiologyQ2 · BIOLOGY

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

Q2 · BIOLOGY

ArticleOA

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

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.

15 Aug 2015·Clinical Cancer ResearchQ1 · MEDICINE

Synergistic Leukemia Eradication by Combined Treatment with Retinoic Acid and HIF Inhibition by EZN-2208 (PEG-SN38) in Preclinical Models of PML-RARα and PLZF-RARα–Driven Leukemia

Q1 · MEDICINE

Article

Author: Coltella, Nadia ; Valsecchi, Roberta ; Ponente, Manfredi ; Bernardi, Rosa ; Ponzoni, Maurilio

AbstractPurpose: Retinoic acid-arsenic trioxide (ATRA-ATO) combination therapy is the current standard of care for patients with acute promyelocytic leukemia (APL) carrying the oncogenic fusion protein PML-RARα. Despite the high cure rates obtained with this drug combination, resistance to arsenic is recently emerging. Moreover, patients with APL carrying the PLZF-RARα fusion protein are partially resistant to ATRA treatment. Hypoxia-inducible factor-1α (HIF-1α) activation has been recently reported in APL, and EZN-2208 (PEG-SN38) is a compound with HIF-1α inhibitory function currently tested in clinical trials. This study investigates the effect of EZN-2208 in different preclinical APL models, either alone or in combination with ATRA.Experimental Design: Efficacy of EZN-2208 in APL was measured in vitro by assessing expression of HIF-1α target genes, cell migration, clonogenicity, and differentiation, vis a vis the cytotoxic and cytostatic effects of this compound. In vivo, EZN-2208 was used in mouse models of APL driven by PML-RARα or PLZF-RARα, either alone or in combination with ATRA.Results: Treatment of APL cell lines with noncytotoxic doses of EZN-2208 causes dose-dependent downregulation of HIF-1α bona fide target genes and affects cell migration and clonogenicity in methylcellulose. In vivo, EZN-2208 impairs leukemia progression and prolongs mice survival in APL mouse models. More importantly, when used in combination with ATRA, EZN-2208 synergizes in debulking leukemia and eradicating leukemia-initiating cells.Conclusions: Our preclinical data suggest that the combination ATRA-EZN-2208 may be tested to treat patients with APL who develop resistance to ATO or patients carrying the PLZF-RARα fusion protein. Clin Cancer Res; 21(16); 3685–94. ©2015 AACR.

01 Oct 2014·Pediatric Blood & CancerQ3 · MEDICINE

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

Q3 · MEDICINE

Article

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

BACKGROUNDEZN-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.PROCEDUREEZN-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.RESULTSThirty 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.CONCLUSIONSEZN-2208 was generally well-tolerated and was associated with clinical benefit in patients with neuroblastoma.

100 Deals associated with Firtecan pegol

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External Link

KEGG	Wiki	ATC	Drug Bank
D10464	-	-	DB14953

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Relapsed Solid Neoplasm	Preclinical	US	Enzon Pharmaceuticals, Inc.	01 Feb 2010
Metastatic breast cancer	Preclinical	US	Enzon Pharmaceuticals, Inc.	01 Nov 2009
Metastatic Colorectal Carcinoma	Preclinical	GB	Enzon Pharmaceuticals, Inc.	01 Jun 2009
Metastatic Colorectal Carcinoma	Preclinical	US	Enzon Pharmaceuticals, Inc.	01 Jun 2009
Metastatic Colorectal Carcinoma	Preclinical	IL	Enzon Pharmaceuticals, Inc.	01 Jun 2009
Metastatic Colorectal Carcinoma	Preclinical	NL	Enzon Pharmaceuticals, Inc.	01 Jun 2009
Metastatic Colorectal Carcinoma	Preclinical	CA	Enzon Pharmaceuticals, Inc.	01 Jun 2009
Advanced Malignant Solid Neoplasm	Preclinical	US	Enzon Pharmaceuticals, Inc.	01 May 2007
Lymphoma	Preclinical	US	Enzon Pharmaceuticals, Inc.	01 May 2007