Delving into the Latest Updates on Dusigitumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Dusigitumab (USAN)

Target

IGF-2

Action

inhibitors

Mechanism

IGF-2 inhibitors(Insulin-like growth factor II inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmMetastatic breast cancerMetastatic hepatocellular carcinoma+ [1]

Originator Organization

MedImmune LLC

Active Organization-

Inactive Organization

MedImmune LLC

AstraZeneca PLC

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9907242H

Source: *****

Sequence Code 9907237L

Source: *****

A Phase 1, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors 1 and 2, in Japanese Subjects With Advanced Solid Tumours Refractory to Standard Therapy or for Which No Standard Therapy Exists

Start Date12 Aug 2011

Sponsor / Collaborator

AstraZeneca PLC

NCT01340040

/ CompletedPhase 1

A Phase 1, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors I and II, in Japanese Subjects With Advanced Solid Tumours Refractory to Standard Therapy or for Which No Standard Therapy Exists

The primary purpose of this study is to explore the safety and tolerability of MEDI-573 in Japanese subjects with advanced solid tumours refractory to standard therapy or for which no standard therapy exists.

Start Date01 Jul 2011

Sponsor / Collaborator

AstraZeneca PLC

[+1]

100 Clinical Results associated with Dusigitumab

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100 Translational Medicine associated with Dusigitumab

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100 Patents (Medical) associated with Dusigitumab

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10

Literatures (Medical) associated with Dusigitumab

01 Apr 2023·Lupus

Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis

Article

Author: Lin, Xiaobing ; Peng, Zhishen ; Liang, Xiaofeng ; Lin, Weiyi ; Wei, Shanshan ; Lin, Zien

Background Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). This study aimed to explore biomarkers, mechanisms, and potential novel agents regarding LN through bioinformatic analysis. Method Four expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were acquired. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses of DEGs were performed using the R software. The protein-protein interaction (PPI) network was developed using the STRING database. Additionally, five algorithms were used to screen out the hub genes. Expression of the hub genes were validated using Nephroseq v5. CIBERSORT was used to evaluate the infiltration of immune cells. Finally, The Drug-Gene Interaction Database was used to predict potential targeted drugs. Result FOS and IGF1 were identified as hub genes, with excellent specificity and sensitivity diagnosis of LN. FOS was also related to renal injury. LN patients had lower activated and resting dendritic cells (DCs) and higher M1 macrophages and activated NK cells than healthy control (HC). FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. The targeted drugs were dusigitumab and xentuzumab target for IGF1. Conclusion We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN.

09 Feb 2017·OncogeneQ1 · MEDICINE

Overproduction of IGF-2 drives a subset of colorectal cancer cells, which specifically respond to an anti-IGF therapeutic antibody and combination therapies

Q1 · MEDICINE

Article

Author: Zhong, H ; Chen, C ; Hollingsworth, R E ; Yao, X ; Huang, J ; Ren, P ; Yao, Y ; Fazenbaker, C ; Herbst, R ; Breen, S

Colorectal cancer (CRC) is a heterogeneous disease with a broad spectrum of genetic and epigenetic changes. A comprehensive molecular characterization of CRC by The Cancer Genome Atlas Network detected the overexpression of the insulin-like growth factor 2 (IGF2) gene, encoding a ligand for the insulin-like growth factor 1 receptor (IGF-1R), in a subset of CRC tumors. In this study, we investigated the oncogenic potential of IGF-2 in IGF2-overexpressing CRC models and the efficacy of MEDI-573, an IGF-1/2-neutralizing antibody. We found that a subset of CRC cell lines express high IGF-2 levels owing to an increased DNA copy number and hypermethylation in the H19 promoter of the IGF2 gene. MEDI-573 efficiently neutralized IGF-2 and induced apoptosis, which resulted in significant tumor growth inhibition in CRC mouse models that express high levels of IGF-2. These effects were specific to CRCs overexpressing IGF-2, as MEDI-573 did not affect the growth CRC cell lines with normal levels. Moreover, blockade of IGF-2 by MEDI-573 modulated other signaling pathways, suggesting combination therapies with inhibitors of these pathways. Indeed, in vivo efficacy was significantly enhanced when MEDI-573 was used in combination with trastuzumab, AZD2014 (dual mTORC1/2i), AZD5363 (AKTi) and selumetinib (AZD6244/ARRY-142886, MEK1/2i) or cetuximab. These results demonstrate that overexpressed IGF-2 is the major tumorigenic driver in a subset of CRCs and encourage testing of MEDI-573, alone and in combinations, in IGF2-overexpressing CRC patients.

01 Oct 2015·Clinical Cancer ResearchQ1 · MEDICINE

Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade

Q1 · MEDICINE

Review

Author: Lovly, Christine M. ; Iams, Wade T.

AbstractThe IGF1R signaling pathway is a complex and tightly regulated network that is critical for cell proliferation, growth, and survival. IGF1R is a potential therapeutic target for patients with many different malignancies. This brief review summarizes the results of clinical trials targeting the IGF1R pathway in patients with breast cancer, sarcoma, and non–small cell lung cancer (NSCLC). Therapeutic agents discussed include both monoclonal antibodies to IGF1R (dalotuzumab, figitumumab, cixutumumab, ganitumab, R1507, AVE1642) and newer IGF1R pathway targeting strategies, including monoclonal antibodies to IGF1 and IGF2 (MEDI-573 and BI 836845) and a small-molecule tyrosine kinase inhibitor of IGF1R (linsitinib). The pullback of trials in patients with breast cancer and NSCLC based on several large negative trials is noted and contrasted with the sustained success of IGF1R inhibitor monotherapy in a subset of patients with sarcoma. Several different biomarkers have been examined in these trials with varying levels of success, including tumor expression of IGF1R and its pathway components, serum IGF ligand levels, alternate pathway activation, and specific molecular signatures of IGF1R pathway dependence. However, there remains a critical need to define predictive biomarkers in order to identify patients who may benefit from IGF1R-directed therapies. Ongoing research focuses on uncovering such biomarkers and elucidating mechanisms of resistance, as this therapeutic target is currently being analyzed from the bedside to bench. Clin Cancer Res; 21(19); 4270–7. ©2015 AACR.

100 Deals associated with Dusigitumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D10352	Dusigitumab	-	DB12363

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Phase 2	France	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Germany	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Canada	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	United Kingdom	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Poland	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Spain	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Israel	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	The Bahamas	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	Belgium	MedImmune LLC	13 Jun 2011
Metastatic breast cancer	Phase 2	United States	MedImmune LLC	13 Jun 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01446159 (CTgov)	Phase 2	Metastatic breast cancer	188	Aromatase inhibitor+MEDI-573 (MEDI-573 30 mg/kg + AI)	sejfdhhgry(shtsfhencr) = wtemtmleto tqgueaszvj (wsgwvcggys, nrnbcubokg - wbxsgptbbk) View more	-	28 Aug 2018
NCT01446159 (CTgov)	Phase 2	Metastatic breast cancer	188	Aromatase inhibitor+MEDI-573 (MEDI-573 45 mg/kg + AI)	sejfdhhgry(shtsfhencr) = bqqdctgsti tqgueaszvj (wsgwvcggys, cjzpxavanc - qdqklpadlf) View more	-	28 Aug 2018
NCT01340040 (Pubmed \| Invest New Drugs) Manual	Phase 1	Advanced Malignant Solid Neoplasm	10	MEDI-573	(hekrkglxtt) = fatigue (n = 2 patients), pyrexia (n = 2), diarrhoea (n = 2) and electrocardiogram QT prolongation (n = 2) ipiejzabvo (eudcbsundx )	Positive	01 Feb 2015

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Translational Medicine

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Deal

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Core Patent

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Dusigitumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation