Delving into the Latest Updates on Codrituzumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

+ [2]

Target

GPC3

Action

inhibitors

Mechanism

GPC3 inhibitors(Glypican-3 inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects), Antibody-dependent cellular phagocytosis (ADCP) effects

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders

Active Indication

Brain CancerGPC3 Positive NeoplasmsHepatocellular Carcinoma

Inactive Indication

Metastatic hepatocellular carcinoma

Originator Organization

Chugai Pharmaceutical Co., Ltd.

Active Organization

Roche Holding AG

Chugai Pharma USA LLC

Inactive Organization

Hoffmann-La Roche, Inc.

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 13592L

Source: *****

Sequence Code 13574H

Source: *****

The purpose of this study to find out whether codrituzumab is a safe treatment that causes few or mild side effects in children and young adults who have solid tumors that express the protein GPC3. The researchers also want to study the way codrituzumab is absorbed, distributed, and cleared from the body.

Start Date09 Jun 2021

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

JPRN-JapicCTI-163325

/ CompletedPhase 1

A PHASE I, OPEN-LABEL, MULTI-CENTER, DOSE-ESCALATION STUDY OF CODRITUZUMAB, AN ANTI-GLYPICAN-3 MONOCLONAL ANTIBODY, IN COMBINATION WITH ATEZOLIZUMAB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA

Start Date01 Aug 2016

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

JPRN-jRCT2080221779

/ Unknown statusPhase 2

A Randomized, Placebo-controlled, Double-blind, Multicenter Phase II Trial of Intravenous GC33 at 1600 mg Q2W in Previously Treated Patients with Unresectable Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Start Date25 Apr 2012

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

100 Clinical Results associated with Codrituzumab

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100 Translational Medicine associated with Codrituzumab

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100 Patents (Medical) associated with Codrituzumab

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23

Literatures (Medical) associated with Codrituzumab

01 Jan 2025·Heliyon

Glypican-3 is a key tuner of the Hedgehog pathway in COPD

Article

Author: Hatoum, Sarah ; Dubernard, Xavier ; Durlach, Anne ; Dormoy, Valérian ; Mérol, Jean-Claude ; Perotin, Jeanne-Marie ; Polette, Myriam ; Petit, Laure M G ; Ancel, Julien ; Delepine, Gonzague ; Ruaux, Christophe ; Devilliers, Maëva A ; Saber Cherif, Lynda ; Deslée, Gaëtan

Hedgehog (HH) pathway is involved in pulmonary development and lung homeostasis. It orchestrates airway epithelial cell (AEC) differentiation and contributes to respiratory pathogenesis. The core elements Gli2, Smo, and Shh were found altered in the bronchial epithelium of patients with chronic obstructive pulmonary disease (COPD). Here, we investigated the co-receptors to fully decipher the complex machinery of airway HH pathway activation in health and COPD. The core elements and co-receptors of HH signalling were investigated in lung cell populations using single-cell RNAseq analysis. The transcript levels of the principal co-receptor GPC3 were investigated on public RNAseq datasets and by RT-qPCR. The localisation of GPC3 was evaluated through immunofluorescent stainings on isolated bronchial AEC and tissues from non-COPD and COPD patients. GPC3 pharmacological modulation was achieved with Codrituzumab during AEC differentiation. We demonstrated that the core elements were not abundant in pulmonary cell populations. Focusing on co-receptors, GPC3 was the most expressed transcript in tracheobronchial epithelial cells. The decrease in GPC3 transcript levels correlated with the severity of airway obstrution in COPD patients. Finally, interfering with GPC3 signalling during AEC differentiation induced downregulation of the HH pathway attested by a decrease of Gli2 leading to reduced ciliogenesis and altered mucin production. GPC3 appears as a crucial co-receptor for the HH pathway in the respiratory context. The modulation of GPC3 may represent a novel experimental strategy to tune HH signalling in therapeutic perspectives.

01 Oct 2023·Molecular Immunology

A novel bispecific antibody as an immunotherapeutic agent in hepatocellular carcinoma

Article

Author: Zhao, Liwen ; Song, Qifeng ; Luo, Cheng ; Wang, Yong ; Xu, Yao ; Wei, Jian ; Liu, Qingxia

Hepatocellular carcinoma (HCC) remains one of the most common and highly fatal malignancies in humans worldwide with increasing prevalence and limited therapeutic options. For many decades, many researchers have attempted to find effective curative methods for HCC and great strides have been made. GPC3 is overexpressed in HCC, but not in normal liver, making it a rational immunotherapeutic target for HCC. GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients. Phase II trials of GC33 to evaluate its efficacy and safety in advanced or metastatic HCC, showed no significant differences in overall survival and progression-free survival compared with the placebo. Retrospective analysis indicates that high drug exposure and high CD16 expression may contribute to the clinical efficacy of GC33. Chugai Pharmaceutical has restarted its Phase I trial of GC33, continuing to explore its clinical value targeting GPC3 in solid tumors. To enhance the antitumor potency of GC33, we designed a GPC3/CD16A bispecific antibody (QDEB). In this study, we obtained QDEB at high purity and assessed its effectiveness in the therapy of HCC compared with GC33. In vitro cytotoxicity assays and in vivo experiments demonstrated that QDEB could enhance anti-tumor efficacy compared with GC33. CD16A activation and increased cytokines release were associated with higher anti-tumor activity. In conclusion, this bispecific antibody may possibly help develop new therapeutic strategies for HCC and develop new treatment options in the future.

01 Aug 2022·Hepatology

Novel low‐avidity glypican‐3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC

Article

Author: Peng, Yibing ; He, Yukai ; He, Aiwu Ruth ; Mao, Rui ; Shi, Huidong ; Zhang, Huajun ; Jiang, Xiaotao ; Qiu, Xiangguo ; Sadek, Ramses ; Hussein, Mohamed S. ; Brody, Pierce ; Kehinde‐Ige, Mercy ; Caraballo Galva, Leidy D.

AbstractBackground and AimsChimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low‐affinity monoclonal antibodies (mAbs) and low‐avidity CARTs for HCC and to test the hypothesis that low‐avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects.Methods and ResultsNew human glypican‐3 (hGPC3) mAbs were developed from immunized mice. We obtained three hGPC3‐specific mAbs that stained HCC tumors, but not the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33, the frequently used high‐affinity mAb, but with approximately 17‐fold lower affinity. We then compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor effects. In vitro, low‐avidity 8F8 CARTs killed both hGPC3high and hGPC3low HCC tumor cells to the same extent as high‐avidity GC33 CARTs. 8F8 CARTs expanded and persisted to a greater extent than GC33 CARTs, resulting in durable responses against HCC xenografts. Importantly, compared with GC33 CARTs, there were 5‐fold more of 8F8‐BBz CARTs in the tumor mass for a longer period of time. Remarkably, the tumor‐infiltrating 8F8 CARTs were less exhausted and apoptotic, and more functional than GC33 CARTs.ConclusionThe low‐avidity 8F8‐BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high‐avidity CARTs.

100 Deals associated with Codrituzumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14843

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic hepatocellular carcinoma	Preclinical	Spain	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	Germany	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	South Korea	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	Singapore	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	Italy	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	New Zealand	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	United Kingdom	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	Hong Kong	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	Belgium	Hoffmann-La Roche, Inc.	02 Feb 2012
Metastatic hepatocellular carcinoma	Preclinical	France	Hoffmann-La Roche, Inc.	02 Feb 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


JPRN-JapicCTI-163325 (ESMO2018)	Phase 1	Metastatic hepatocellular carcinoma	20	Codrituzumab 1600mg	(bgmkdgibxu) = 0% vs 15% vs 0% cqdpnkrzkc (tgcoqumnfn ) View more	Positive	21 Oct 2018
				Atezolizumab 1200mg
NCT01507168 (Pubmed \| J Hepatol) Manual	Phase 2	Advanced Hepatocellular Carcinoma	185	codrituzumab	(fgzudiqdbc) = bzwwnwqeti vnfliwzhdg (oiafzofirb ) View more	Negative	01 Aug 2016
				Placebo	(fgzudiqdbc) = xfmoqrjhyy vnfliwzhdg (oiafzofirb ) View more
NCT01507168 (ASCO2014)	Phase 2	Unresectable Hepatocellular Carcinoma	185	GC33 1600 mg	(nttdvygllc) = kbxhssxyja btudstoxlx (ymfmwohpio ) View more	-	20 May 2014
				Placebo	(nttdvygllc) = vqmxoubzdm btudstoxlx (ymfmwohpio ) View more

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Translational Medicine

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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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Codrituzumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation