Delving into the Latest Updates on Tigatuzumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

DR5

Action

agonists

Mechanism

DR5 agonists(Tumor necrosis factor receptor superfamily member 10B agonists), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Metastatic Colorectal Carcinoma

Inactive Indication

Advanced Hepatocellular CarcinomaAdvanced Malignant Solid NeoplasmLymphoma+ [5]

Originator Organization

The University of Alabama at Birmingham

Active Organization

Ludwig Institute for Cancer Research Ltd.

Austin Health

Daiichi Sankyo Co., Ltd.

Inactive Organization

Daiichi Sankyo, Inc.

The University of Alabama at Birmingham

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 11369H

Source: *****

Sequence Code 11377L

Source: *****

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American women. Metastatic disease including metastatic breast cancer unfortunately remains incurable. One reason is due to the inability to develop specific therapies for specific cancer subsets.
The use of modern genomic techniques has significantly enhanced our recent understanding of breast cancer biology. Five distinct breast cancer subsets have been recognized, one of which is basal-like breast cancer. Basal-like breast cancer is typically estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER-2-Neu) negative. This is referred to as triple negative breast cancer or TBNC. TBNC represents a significant proportion of breast cancer patients (10-20%) and has a poor prognosis with no targeted approach to therapy as of yet.
Tigatuzumab is a humanized monoclonal antibody targeting a death receptor on the breast cancer cells. Previous studies have shown that combining antibodies with selected chemotherapy agents have induced tumor cell death. The hypothesis of this study is to use tigatuzumab and combine it with Abraxane to serve as a targeting agent in metastatic TBNC patients.

Start Date01 Mar 2011

Sponsor / Collaborator

The University of Alabama at Birmingham

[+3]

NCT01220999

/ CompletedPhase 1IIT

A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer

This was a Phase 1, open-label, single-center study of CS-1008, an immunoglobulin G subclass 1 (IgG1) humanized monoclonal antibody, in subjects with advanced colorectal carcinoma who had received ≥ 1 prior chemotherapy regimen for metastatic disease. Primary study objectives were to determine the influence of the CS-1008 dose on the biodistribution, pharmacokinetics (PK) and tumor uptake of radiolabeled CS-1008 following a single infusion and following continuous sequential doses of CS-1008. Secondary objectives were to evaluate changes in tumor metabolism, antitumor response, and changes in serum apoptosis biomarkers and tumor response markers following treatment with CS-1008.

Start Date12 Oct 2010

Sponsor / Collaborator

Ludwig Institute for Cancer Research Ltd.

[+1]

NCT01033240

/ CompletedPhase 2

Clinical Study Protocol Phase 2, Randomized Study of CS-1008 in Combination With Sorafenib Compared to Sorafenib Alone as First-Line Systemic Therapy in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to determine the safety and efficacy of CS-1008 in combination with sorafenib to sorafenib alone for treating liver cancer. Approximately 160 participants will take part in this study at approximately 22 sites (4 in the US, 8 in Japan, and 10 in Asia).

Start Date09 Jul 2010

Sponsor / Collaborator

Daiichi Sankyo, Inc.

100 Clinical Results associated with Tigatuzumab

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100 Translational Medicine associated with Tigatuzumab

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100 Patents (Medical) associated with Tigatuzumab

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65

Literatures (Medical) associated with Tigatuzumab

01 Dec 2023·Pharmacological Research

Neutrophils as potential therapeutic targets for breast cancer

Review

Author: Zhang, Li-Jun ; Jin, Jin-Mei ; Chen, Xin-Yi ; Gong, Yi-Ting ; Liu, Yi-Chen ; Zhang, Wei-Dong ; Chen, Yi-Xu ; Luan, Xin ; Lin, Jia-Yi ; Tang, Min ; Yan, Yue

Breast cancer (BC) remains the foremost cause of cancer mortality globally, with neutrophils playing a critical role in its pathogenesis. As an essential tumor microenvironment (TME) component, neutrophils are emerging as pivotal factors in BC progression. Growing evidence has proved that neutrophils play a Janus- role in BC by polarizing into the anti-tumor (N1) or pro-tumor (N2) phenotype. Clinical trials are evaluating neutrophil-targeted therapies, including Reparixin (NCT02370238) and Tigatuzumab (NCT01307891); however, their clinical efficacy remains suboptimal. This review summarizes the evidence regarding the close relationship between neutrophils and BC, emphasizing the critical roles of neutrophils in regulating metabolic and immune pathways. Additionally, we summarize the existing therapeutic approaches that target neutrophils, highlighting the challenges, and affirming the rationale for continuing to explore neutrophils as a viable therapeutic target in BC management.

01 Aug 2021·Journal of the European Academy of Dermatology and Venereology

Efficacy and safety of tildrakizumab 100 mg for plaque psoriasis in patients randomized to treatment continuation vs treatment withdrawal with retreatment upon relapse in reSURFACE 1

Letter

Author: Rozzo, S.J. ; Liao, W. ; Cantrell, W. ; Mendelsohn, A.M. ; Lee, P.

Chronic moderate-to-severe plaque psoriasis frequently requires long-term biol. treatment, but treatment gaps resulting in relapse are not uncommon.Tildrakizumab is a high-affinity, humanized, IgG1kappa, anti-interleukin-23p19 monoclonal antibody approved to treat plaque psoriasis.This study focus on adult patients with moderate-to-severe plaque psoriasis required tildrakizumab-treated patients who achieved ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75; responders) at Week 28 to be rerandomized to either continued tildrakizumab treatment or withdrawal (placebo) with retreatment with their initial dose of tildrakizumab upon relapse.Of 116 patients continuously treated with tildrakizumab 100 mg after Week 28, 92.6%, 81.5% and 49.6% achieved PASI 50, PASI 75 and PASI 90, resp., at Week 64.From Weeks 28 - 64 of reSURFACE 1, tildrakizumab 100 mg was well tolerated and efficacious in patients receiving continuous treatment; patients withdrawn to placebo recovered response within a median of 28 days.The durability of tildrakizumab responses and rapid regain of efficacy after relapse and retreatment support long-term clin. use of tildrakizumab for the treatment of moderate-to-severe psoriasis.

01 Nov 2020·Cancer LettersQ1 · MEDICINE

Oral recombinant methioninase increases TRAIL receptor-2 expression to regress pancreatic cancer in combination with agonist tigatuzumab in an orthotopic mouse model

Q1 · MEDICINE

Article

Author: Tan, Yuying ; Hoffman, Robert M ; Bouvet, Michael ; Yamamoto, Jun ; Miyake, Kentaro ; Singh, Shree Ram ; Inubushi, Sachiko ; Sugisawa, Norihiko ; Nishino, Hiroto ; Chawla, Sant P ; Homma, Yuki ; Matsuyama, Ryusei ; Tashiro, Yoshihiko ; Endo, Itaru ; Han, Qinghong ; Higuchi, Takashi

Methionine addiction is a fundamental and general hallmark of cancer. Gene expression analysis showed that methionine restriction (MR) of methionine-addicted cancer cells increases TNF-related apoptosis-induced ligand receptor-2 (TRAIL-R2) expression. Here, we determined the effects of MR on TRAIL-R2 targeted therapy in pancreatic cancer by the TRAIL-R2 agonist tigatuzumab. Human pancreatic cancer cell lines were cultured in control or methionine-free medium. The effects of MR on TRAIL-R2 expression and sensitivity to tigatuzumab were evaluated in vitro. An orthotopic pancreatic cancer mouse model was established to evaluate the efficacy of MR using oral recombinant methioninase (o-rMETase), and the efficacy of tigatuzumab and their combination. MR enabled tigatuzumab-induced apoptosis, by increasing TRAIL-R2 expression in pancreatic cancer cells in vitro. The protein expression level of the melanoma-associated antigen MAGED2, which reduces TRAIL-R2 expression, was decreased by MR. In the orthotopic pancreatic cancer mouse model, o-rMETase increased TRAIL-R2 expression level in the tumors and enabled the antitumor efficacy of tigatuzumab. MR, effected by o-rMETase, enabled the efficacy of the TRAIL-R2 agonist tigatuzumab by increasing TRAIL-R2 expression in pancreatic cancer. Our results suggest that o-rMETase has clinical potential for treating pancreatic cancer.

100 Deals associated with Tigatuzumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Tigatuzumab	-	DB15101

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 1	United Kingdom	Daiichi Sankyo, Inc.	01 Jul 2009
Metastatic breast cancer	Discovery	United States	The University of Alabama at Birmingham	01 Mar 2011
Advanced Hepatocellular Carcinoma	Discovery	South Korea	Daiichi Sankyo, Inc.	09 Jul 2010
Advanced Hepatocellular Carcinoma	Discovery	United States	Daiichi Sankyo, Inc.	09 Jul 2010
Advanced Hepatocellular Carcinoma	Discovery	Japan	Daiichi Sankyo, Inc.	09 Jul 2010
Advanced Hepatocellular Carcinoma	Discovery	Taiwan Province	Daiichi Sankyo, Inc.	09 Jul 2010
Ovarian Cancer	Discovery	United States	Daiichi Sankyo, Inc.	06 Oct 2009
Metastatic Colorectal Carcinoma	Discovery	United Kingdom	Daiichi Sankyo, Inc.	01 Jul 2009
Non-small cell lung cancer stage IIIA	Discovery	Germany	Daiichi Sankyo Co., Ltd.	01 Jun 2009
Pancreatic carcinoma non-resectable	Discovery	United States	Daiichi Sankyo, Inc.	15 Aug 2007

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Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01033240 (CTgov)	Phase 2	Advanced Hepatocellular Carcinoma	172	Sorafenib (Sorafenib)	(mlzvecctpf) = fqokzdcufu eaxykxlxci (kigirwkpdh, sdnfftmrxt - hzbbupakxz) View more	-	08 Apr 2021
				CS-1008+Sorafenib (CS-1008 6/2 mg/kg + Sorafenib)	(mlzvecctpf) = qnjtuoqrmr eaxykxlxci (kigirwkpdh, zudszusmyz - lketvawiaq) View more
NCT00521404 (CTgov)	Phase 2	Pancreatic carcinoma non-resectable	65	CS-1008 (humanized anti-DR5 antibody)+gemcitabine	jglvzzmdkq(csgydgcjsc) = enipretyvc aoffujbklp (rnqxrzxats, gmvcfjnjui - trmydnpgoc) View more	-	03 Dec 2020
NCT00945191 (CTgov)	Phase 2	Ovarian Cancer	24	CS-1008+Carboplatin+Paclitaxel	mkshsbinqv(zdyaongpcc) = fszenrhpxm rrfpbnahon (elgemdsgme, cflbesshyi - vstgsiyaow) View more	-	18 Nov 2020
NCT01220999 (CTgov)	Phase 1	Metastatic Colorectal Carcinoma	19	CS-1008 (Cohort 1)	upvrmnuucn(jtnksfiwmp) = bdwxvlmwod kzfevaappr (qqejwnajdz, pycrxdqigo - znozzeqcxy) View more	-	23 Sep 2019
				CS-1008 (Cohort 2)	upvrmnuucn(jtnksfiwmp) = quxaxadkqd kzfevaappr (qqejwnajdz, yqkqusdvve - gaszxokuhb) View more
NCT01307891 (TBCRC 019, CTgov)	Phase 2	Metastatic breast cancer \| Metastatic Triple-Negative Breast Carcinoma	64	Tigatuzumab+Abraxane (Abraxane + Tigatuzumab)	(ctzkptlhhk) = zdavisoeoc bqkyljpzvv (tpobjmpsld, vagfzcjjth - uqnarrzxog) View more	-	13 Sep 2017
				Abraxane alone (Abraxane Alone)	(ctzkptlhhk) = tuxnieoyyy bqkyljpzvv (tpobjmpsld, laalaefgcm - xlhqfhduzm) View more
NCT01220999 (Pubmed \| J Urol \| J Clin Oncol) Manual	Phase 1	Metastatic Colorectal Carcinoma	19	CS-1008	(ocjwvulkuk) = osgrsnahlc arcjoilayh (labloqdixn ) View more	Positive	20 Aug 2015
NCT01307891 (TBCRC 019, Pubmed \| Clin Cancer Res) Manual	Phase 2	Triple Negative Breast Cancer Triple-Negative	60	Nanoparticle Albumin-Bound Paclitaxel+Tigatuzumab	(vhzvtwemjj) = djpeprcvck qsnptvrzbq (uytninantr ) View more	Negative	15 Jun 2015
				Nanoparticle Albumin-Bound Paclitaxel	(vhzvtwemjj) = adftamszgm qsnptvrzbq (uytninantr ) View more
ASTRO2013	Not Applicable	Brain Stem Neoplasms	4	Radiation Therapy (RT)	emcrepfrjz(muasdzrqvq) = amsexdlmfu ilrsmdhoef (dwkanqbghe )	Positive	01 Oct 2013
				Temozolomide (TMZ)	emcrepfrjz(muasdzrqvq) = umvhykbavc ilrsmdhoef (dwkanqbghe )
NCT01220999 (ASCO2013)	Phase 1	Metastatic Colorectal Carcinoma	19	CS-1008	(egpmdzjhau) = xbqrvpkynk coolrlfkua (fngbtavsrs ) View more	-	20 May 2013
ASCO2012	Phase 2	metastatic non-small cell lung cancer	100	Tigatuzumab	(tnzfimakyx) = ajuggrlpxy axddhsclwc (btvxciehmv, 3.3 - 6.6) View more	Negative	20 May 2012
				Placebo	(tnzfimakyx) = nnrtcbetgk axddhsclwc (btvxciehmv, 4.1 - 5.8) View more

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Translational Medicine

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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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Tigatuzumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation