Delving into the Latest Updates on ERY-974 with Synapse

Overview

Basic Info

Drug Type

Bispecific T-cell Engager (BiTE)

Synonyms

T cell redirecting bispecific antibody

Target

CD3 x GPC3

Mechanism

CD3 modulators(T cell surface glycoprotein CD3 modulators), GPC3 modulators(Glypican-3 modulators)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Metastatic hepatocellular carcinoma

Inactive Indication

Advanced Malignant Solid Neoplasm

Originator Organization

Chugai Pharmaceutical Co., Ltd.

Active Organization

Chugai Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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This is a multicenter, open-label, dose-escalation study designed to determine the maximum tolerated dose (MTD) by evaluating dose-limiting toxicities (DLTs) and to evaluate the safety, tolerability, pharmacokinetics, anti-tumor effect, and biomarkers of ERY974 in combination with atezolizumab and bevacizumab following premedication with tocilizumab in patients with locally advanced or metastatic HCC.

Start Date01 Jun 2021

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

JPRN-jRCT2080224729 / RecruitingPhase 1

A PHASE I STUDY OF ERY974 AS A SINGLE AGENT IN PATIENTS WITH GPC3-POSITIVE ADVANCED SOLID TUMORS

Start Date07 Nov 2019

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

JPRN-JapicCTI-194805 / RecruitingPhase 1

A PHASE I STUDY OF ERY974 AS A SINGLE AGENT IN PATIENTS WITH GPC3-POSITIVE ADVANCED SOLID TUMORS

Start Date07 Nov 2019

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

100 Clinical Results associated with ERY-974

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100 Translational Medicine associated with ERY-974

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100 Patents (Medical) associated with ERY-974

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8

Literatures (Medical) associated with ERY-974

01 Apr 2022·Toxicology and Applied PharmacologyQ3 · MEDICINE

Priming treatment with T-cell redirecting bispecific antibody ERY974 reduced cytokine induction without losing cytotoxic activity in vitro by changing the chromatin state in T cells

Q3 · MEDICINE

Article

Author: Mishima, Masayuki ; Iwata, Yoshika ; Narushima, Yuta ; Harada, Asako

CD3 bispecific constructs are anticipated to become an important form of cancer immunotherapy, but they frequently cause cytokine release syndrome (CRS) that is difficult to manage in clinical contexts. A combination of intra-patient dose escalation and immunosuppressive treatment is widely used to mitigate CRS. Studies suggest that CRS after subsequent doses of CD3 bispecific constructs is less severe than after the priming dose, and that step-up dosing reduces cytokine levels in animals and humans. However, the mechanism underlying the reduced cytokine induction after priming treatment with CD3 bispecific constructs is unclear. To understand human T-cell activation and chromatin states after priming treatment with CD3 bispecific construct targeting CD3ɛ and glypican 3 (ERY974), we examined cytokine levels, cytokine mRNA expression, CD3ɛ expression, CD3-mediated signal transduction, T cell activation markers, cytotoxicity against target cells, and chromatin states in T cells after ERY974 priming treatment or negative control. The second ERY974 treatment decreased cytokines on Day 8, and ERY974 priming treatment changed the chromatin state in T cells. CD3ɛ expression, CD3-mediated signal transduction, T cell activation markers, and cytotoxicity were similar between the priming treatment with ERY974 and negative control. The present study suggests that chromatin state changes in T cells after the priming treatment was a pivotal factor in the mitigation of cytokine release after the second ERY974 treatment.

01 Aug 2020·Toxicology in VitroQ3 · MEDICINE

In vitro toxicological support to establish specification limit for anti-CD3 monospecific impurity in a bispecific T cell engager drug, ERY974

Q3 · MEDICINE

Article

Author: Mishima, Masayuki ; Sano, Yuji ; Wakabayashi, Tetsuya ; Ikuno, Tatsuya ; Iwata, Yoshika ; Harada, Asako ; Shiraiwa, Hirotake ; Shioda, Akifumi

An emerging structure for anti-tumor antibody drugs utilizes a bispecific antibody (BiAb) that recognizes a tumor surface antigen and CD3 on T cells. An impurity that commonly contaminates these BiAb products is an anti-CD3 monoclonal antibody (mAb). The most plausible cause of toxic activity by an anti-CD3 mAb is the induction of cytokines via T cell activation. In this in vitro study, we compared cytokine induction and T cell activation after treatment with an anti-glypican-3/CD3 BiAb (ERY974), anti-CD3 mAb impurity (aCD3), or ERY974 spiked with 5% aCD3. We found that contamination with up to 5% aCD3 did not affect cytokine release by ERY974. Cytokine levels induced by ERY974 in the presence of target cells were significantly higher than those induced by aCD3, but were very similar to those by the spiked treatment. The results supported the specification of a 5% limit for aCD3. OKT-3 had much higher activity to induce cytokines from peripheral blood mononuclear cells in an in vitro assay than aCD3. This suggests that specification limit should be decided for each type of anti-CD3 impurity that affects T cell-activating BiAb drug products. In vitro cytokine assays can provide useful information for determining these specification limits.

01 Mar 2020·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Preclinical PET imaging of bispecific antibody ERY974 targeting CD3 and glypican 3 reveals that tumor uptake correlates to T cell infiltrate

Q2 · MEDICINE

ArticleOA

Author: Schröder, Carolina P ; Sano, Yuji ; Lub-de Hooge, Marjolijn N ; Ishiguro, Takahiro ; Giesen, Danique ; de Vries, Elisabeth Ge ; Sugaya, Naofumi ; Waaijer, Stijn Jh

BackgroundBispecific antibodies redirecting T cells to the tumor obtain increasing interest as potential cancer immunotherapy. ERY974, a full-length bispecific antibody targeting CD3ε on T cells and glypican 3 (GPC3) on tumors, has been in clinical development However, information on the influence of T cells on biodistribution of bispecific antibodies, like ERY974, is scarce. Here, we report the biodistribution and tumor targeting of zirconium-89 (89Zr) labeled ERY974 in mouse models using immuno-positron emission tomography (PET) imaging.MethodsTo study both the role of GPC3 and CD3 on the biodistribution of [89Zr]Zr-N-suc-Df-ERY974,89Zr-labeled control antibodies targeting CD3 and non-mammalian protein keyhole limpet hemocyanin (KLH) or KLH only were used. GPC3 dependent tumor targeting of [89Zr]Zr-N-suc-Df-ERY974 was tested in xenograft models with different levels of GPC3 expression. In addition, CD3 influence on biodistribution of [89Zr]Zr-N-suc-Df-ERY974 was evaluated by comparing biodistribution between tumor-bearing immunodeficient mice and mice reconstituted with human immune cells using microPET imaging and ex vivo biodistribution. Ex vivo autoradiography was used to study deep tissue distribution.ResultsIn tumor-bearing immunodeficient mice, [89Zr]Zr-N-suc-Df-ERY974 tumor uptake was GPC3 dependent and specific over [89Zr]Zr-N-suc-Df-KLH/CD3 and [89Zr]Zr-N-suc-Df-KLH/KLH. In mice engrafted with human immune cells, [89Zr]Zr-N-suc-Df-ERY974 specific tumor uptake was higher than in immunodeficient mice. Ex vivo autoradiography demonstrated a preferential distribution of [89Zr]Zr-N-suc-Df-ERY974 to T cell rich tumor tissue. Next to tumor, highest specific [89Zr]Zr-N-suc-Df-ERY974 uptake was observed in spleen and lymph nodes.Conclusion[89Zr]Zr-N-suc-Df-ERY974 can potentially be used to study ERY974 biodistribution in patients to support drug development.

100 Deals associated with ERY-974

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 3	US	Chugai Pharmaceutical Co., Ltd.	01 Aug 2016
Advanced Malignant Solid Neoplasm	Phase 3	NL	Chugai Pharmaceutical Co., Ltd.	01 Aug 2016
Advanced Malignant Solid Neoplasm	Phase 3	FR	Chugai Pharmaceutical Co., Ltd.	01 Aug 2016
Metastatic hepatocellular carcinoma	Phase 1	JP	Chugai Pharmaceutical Co., Ltd.	01 Jun 2021
Metastatic hepatocellular carcinoma	Phase 1	TW	Chugai Pharmaceutical Co., Ltd.	01 Jun 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05022927 \| JPRN-JapicCTI-194805 (Pubmed)	Phase 1	-	-	ERY974	sdndklcvsa(tcclhsnbjn) = fgjemvrpsk vbsqbootor (dthdpgpfqk )	-	19 Jul 2022
NCT02748837 (AACR2021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	29	ERY 974	(jqutnmanay) = The Grade 3 CRS was associated with Grade 3 transaminitis and a Grade 3 elevation of bilirubin. Both CRS events led to dose delay and dose reduction. shdlabnyim (xbrnwcpcqq ) View more	Positive	10 Apr 2021