Brentuximab Vedotin Overview

Introduction of Brentuximab Vedotin

Brentuximab vedotin (trade name Adcetris) is an antibody-drug conjugate (ADC) medication consisting of the monoclonal antibody cAC10 and the cytotoxic agent MMAE used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). cAC10 (SGN-30) is a chimeric anti-CD30 monoclonal antibody that is derived from the fusion of the variable heavy and light region of the murine anti-CD30 antibody AC10, with the constant γ1-heavy and κ-light region of the human immunoglobulin. MMAE is a synthetic derivative of dolastatin 10, a cytostatic pseudopeptide isolated from the marine shell-less mollusk Dorabella auricularia. MMAE has the effect of cytostasis, tubulin-dependent GTP hydrolysis, and polymerization. Brentuximab vedotin was initially approved in 2011. In January 2012, the drug label was revised with a boxed warning of a condition known as progressive multifocal leukoencephalopathy and death due to opportunistic JC virus infection post treatment. The U.S. Food and Drug Administration approved Adcetris in March 2018 to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.

Mechanism of Action of Brentuximab Vedotin

Hodgkin Lymphoma (HL) accounts for10% of all lymphomas and 0.6% of all cancers in the developed world. HL is histologically defined by rare mononuclear Hodgkin cells and multinucleated Reed-Stemberg (HRS) cells residing in a sea of inflammatory cells. HRS cells are derived from germinal center B cells, but phenotypically lose the expression of typical B cell markers. Despite an excellent cure rate with modern frontline HL therapy, approximately 15% to 20% of patients are not cured with first line or second line therapy and will require additional treatments. HRS cells are characterized by the expression of CD30 receptors. CD30 is a transmembrane glycoprotein that belongs to the tumor necrosis factor (TNF) receptor superfamily. In normal tissue, CD30 expression is restricted to activated T and activated B cells which makes it an ideal therapeutic target for monoclonal antibodies. Brentuximab vedotin is an antibody-drug conjugate (ADC) that was developed by conjugating the tubulin toxin monomethyl auristatin E (MMAE) to the chimeric monoclonal anti-CD30 antibody cAC10. On average, four molecules of MMAE are conjugated to one cAC10. After binding to CD30, brentuximab vedotin in internalized and processed into lysosomal vesicles leading to the release of MMAE from the antibody by reduction or acid hydrolysis within the lysosomes. Subsequently, MMAE is released into cytoplasm and inhibits microtubule polymerization leading to cell cycle arrest followed by cell death. As HRS cells die, a small amount of MMAE is released into the tumor microenvironment which can kill neighboring cells by a CD30-independent manner.

Mechanism of Action of Brentuximab vedotin

Fig 1. Mechanism of Action of Brentuximab vedotin

Table 1. Clinical Projects of Brentuximab vedotin*

NCT ID Status Conditions Lead Sponsor Update Time
NCT03007030 Recruiting Lung Diseases Due to External Agents, Mesothelioma M.D. Anderson Cancer Center December 30, 2016
NCT02388490 Active, not recruiting Relapsed or Refractory EBV-and CD30-positive Lymphomas Seoul National University Hospital March 17, 2015
NCT03302728 Not yet recruiting Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Hodgkin Lymphoma Peter MacCallum Cancer Centre, Australia October 5, 2017
NCT02164006 Active, not recruiting Hodgkin's Lymphoma TG Therapeutics, Inc. June 16, 2014
NCT03474133 Not yet recruiting Hodgkin's Lymphoma Federal Research Institute of Pediatric Hematology, Oncology and Immunology March 22, 2018
NCT02497131 Recruiting Lymphatic Diseases Fondazione Italiana Linfomi ONLUS July 14, 2015
NCT01990534 Active, not recruiting Hodgkin Lymphoma Millennium Pharmaceuticals, Inc. November 21, 2013
NCT03729609 Recruiting Untreated CD30-Positive Hodgkin's Lymphoma Takeda November 2, 2018
NCT01909934 Recruiting Anaplastic Large-cell Lymphoma Millennium Pharmaceuticals, Inc. July 29, 2013
NCT03587844 Recruiting Mycosis Fungoides, Lymphomatoid Papulosis, Sezary Syndrome Memorial Sloan Kettering Cancer Center July 16, 2018
NCT02462538 Active, not recruiting ALK+ Anaplastic Large Cell Lymphoma Arbeitsgemeinschaft medikamentoese Tumortherapie June 4, 2015
NCT02939014 Active, not recruiting Hodgkin Disease, Lymphoma, Large-Cell, Anaplastic Takeda October 19, 2016
NCT01700751 Active, not recruiting Leukemia, Acute Myeloid; Leukemia, Lymphoblastic,Acute; Myelodysplastic Syndromes Washington University School of Medicine October 4, 2012
NCT02572167 Active, not recruiting Hodgkin Lymphoma Seattle Genetics, Inc. October 8, 2015
NCT02429375 Active, not recruiting Hodgkin Lymphoma Memorial Sloan Kettering Cancer Center April 29, 2015
NCT02227433 Active, not recruiting Hodgkin Lymphoma Fondazione Italiana Linfomi ONLUS August 28, 2014
NCT02588651 Recruiting T-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Hepato-splenic T-cell Lymphoma, Adult T-cell Leukemia/Lymphoma, Enteropathy Associated T-cell Lymphoma, NK T-cell Lymphoma, Transformed Mycosis Fungoides Deepa Jagadeesh October 28, 2015
NCT03222492 Recruiting Diffuse Cutaneous Systemic Sclerosis, Scleroderma, dcSSc National Institute of Allergy and Infectious Diseases (NIAID) July 19, 2017
NCT02979522 Recruiting Hodgkin Disease Millennium Pharmaceuticals, Inc. December 1, 2016
NCT03187210 Recruiting Lymphoma University Hospital Inselspital, Berne June 14, 2017
NCT03496779 Recruiting Refractory Peripheral T-Cell Lymphoma, Relapsed Peripheral T-Cell Lymphoma The Lymphoma Academic Research Organisation April 12, 2018
NCT02689219 Recruiting Germ Cell Tumors, Testis Cancer, Testicular Cancer, Embryonal Carcinoma, Nonseminomatous Germ Cell Tumor Costantine Albany February 23, 2016
NCT03198689 Not yet recruiting Diffuse Cutaneous Systemic Sclerosis Lawson Health Research Institute June 26, 2017
NCT01508312 Active, not recruiting Hodgkin's Lymphoma Memorial Sloan Kettering Cancer Center January 11, 2012
NCT01657331 Active, not recruiting Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma Owen A. O'Connor August 6, 2012
NCT02581631 Recruiting Non-Hodgkin's Disease Bristol-Myers Squibb October 21, 2015
NCT01780662 Active, not recruiting Recurrent Adult Hodgkin Lymphoma, Recurrent Childhood Hodgkin Lymphoma, Refractory Childhood Hodgkin Lymphoma National Cancer Institute (NCI) January 31, 2013
NCT03356054 Not yet recruiting DLBCL Stichting Hemato-Oncologie voor Volwassenen Nederland November 29, 2017
NCT01100502 Active, not recruiting Disease, Hodgkin Seattle Genetics, Inc. April 9, 2010
NCT02254239 Active, not recruiting Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma Mayo Clinic October 1, 2014
NCT02467946 Recruiting Clinical Efficacy, Safety Centre Antoine Lacassagne June 10, 2015
NCT01578967 Active, not recruiting Hodgkin Lymphoma, Adult UNC Lineberger Comprehensive Cancer Center April 17, 2012
NCT02086604 Active, not recruiting Lymphoma, Large B-Cell, Diffuse Washington University School of Medicine March 13, 2014
NCT03373305 Not yet recruiting CD30-Positive Neoplastic Cells Present, Folliculotropic Mycosis Fungoides, Recurrent Mycosis Fungoides, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory Mycosis Fungoides, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Sezary Syndrome City of Hope Medical Center December 14, 2017
NCT03409432 Recruiting Lymphomatoid Papulosis, Primary Cutaneous Anaplastic Large Cell Lymphoma, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage I Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage II Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma Basem William, MD January 24, 2018
NCT01830777 Active, not recruiting Acute Myelogenous Leukemia Massachusetts General Hospital April 12, 2013
NCT02729961 Recruiting Anaplastic Large Cell Lymphoma, ALK-Positive, CD30-Positive Neoplastic Cells Present, Systemic Anaplastic Large Cell Lymphoma University of Washington April 6, 2016
NCT01352520 Active, not recruiting CD-30 Positive Anaplastic Large T-cell Cutaneous Lymphoma, Lymphoma, Primary Cutaneous Anaplastic Large Cell, Lymphomatoid Papulosis, Mycosis Fungoides, Skin Lymphoma, Cutaneous Lymphomas, Lymphoma, Hematologic Disorder M.D. Anderson Cancer Center May 12, 2011
NCT02298257 Active, not recruiting HIV Infection, HIV-associated Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma The Lymphoma Academic Research Organisation November 21, 2014
NCT03057795 Recruiting Classical Hodgkin Lymphoma, Hematopoietic Cell Transplantation Recipient, Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma City of Hope Medical Center February 20, 2017
NCT02758717 Recruiting Ann Arbor Stage IB Hodgkin Lymphoma, Ann Arbor Stage II Hodgkin Lymphoma, Ann Arbor Stage IIA Hodgkin Lymphoma, Ann Arbor Stage IIB Hodgkin Lymphoma, Ann Arbor Stage III Hodgkin Lymphoma, Ann Arbor Stage IIIA Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IV Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma, Ann Arbor Stage IVB Hodgkin Lymphoma, Classic Hodgkin Lymphoma Academic and Community Cancer Research United May 2, 2016
NCT02499627 Recruiting Lymphatic Diseases Fondazione Italiana Linfomi ONLUS July 16, 2015
NCT02616965 Recruiting Cutaneous T-cell Lymphoma (CTCL) Fox Chase Cancer Center November 30, 2015
NCT03652441 Not yet recruiting Classical Hodgkin Lymphoma University of Cologne August 29, 2018
NCT02684292 Active, not recruiting Hodgkin Lymphoma Merck Sharp & Dohme Corp. February 17, 2016
NCT03138499 Recruiting Hodgkin's Disease Bristol-Myers Squibb May 3, 2017
NCT01716806 Recruiting Hodgkin Disease Seattle Genetics, Inc. October 30, 2012
NCT02744612 Recruiting Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma City of Hope Medical Center April 20, 2016
NCT01703949 Recruiting CD30-Positive Neoplastic Cells Present, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma University of Washington October 11, 2012
NCT03264131 Recruiting Lymphoma, Adult T-Cell Leukemia/Lymphoma, Lymphatic Diseases UNC Lineberger Comprehensive Cancer Center August 28, 2017
NCT02280993 Active, not recruiting Hodgkin Lymphoma, Refractory, Relapse Marjolein Spiering November 3, 2014
NCT02822586 Active, not recruiting Mycosis Fungoides, Sézary Syndrome Virginia Commonwealth University July 4, 2016
NCT03013933 Recruiting Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, CD30-Positive Neoplastic Cells Present City of Hope Medical Center January 9, 2017
NCT01771107 Active, not recruiting AIDS-Related Hodgkin Lymphoma, Ann Arbor Hodgkin Lymphoma, Classic Hodgkin Lymphoma, HIV Infection National Cancer Institute (NCI) January 18, 2013
NCT02686346 Active, not recruiting Hodgkin Disease The Lymphoma Academic Research Organisation February 19, 2016
NCT02298283 Active, not recruiting Hodgkin Lymphoma The Lymphoma Academic Research Organisation November 21, 2014
NCT01777152 Active, not recruiting Anaplastic Large-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma Seattle Genetics, Inc. January 28, 2013
NCT02227199 Recruiting Recurrent Adult Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, TNFRSF8 Positive University of Washington August 28, 2014
NCT01896999 Recruiting Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma National Cancer Institute (NCI) July 11, 2013
NCT02927769 Recruiting Hodgkin Disease Bristol-Myers Squibb October 7, 2016
NCT03712202 Recruiting Ann Arbor Hodgkin Lymphoma, Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma City of Hope Medical Center October 19, 2018
NCT02191930 Recruiting Hodgkin Lymphoma University of Cologne July 16, 2014
NCT03440788 Not yet recruiting Relapsed or Refractory Hodgkin's Lymphoma Multinational Center for Quality of Life Research, Russia February 21, 2018
NCT01994850 Active, not recruiting CD30 Positive Primary Mediastinal Large B-cell Lymphoma, CD30 Positive Diffuse Large B-cell Lymphoma or CD30 Positive Grey Zone Lymphoma Abramson Cancer Center of the University of Pennsylvania November 26, 2013
NCT02734771 Recruiting Diffuse Large B-Cell Lymphoma Patrick Reagan April 12, 2016
NCT03646123 Recruiting Hodgkin Lymphoma Seattle Genetics, Inc. August 24, 2018
NCT01476410 Active, not recruiting Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma Northwestern University November 22, 2011
NCT03217643 Recruiting Enteropathy Associated T-cell Lymphoma Imagine Institute July 14, 2017
NCT03113500 Recruiting Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative, Anaplastic Large Cell Lymphoma, ALK-Positive, Angioimmunoblastic T-Cell Lymphoma, CD30-Positive Neoplastic Cells Present, Enteropathy-Associated T-Cell Lymphoma, Hepatosplenic T-Cell Lymphoma, Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Peripheral T-Cell Lymphoma, Not Otherwise Specified, Stage III Anaplastic Large Cell Lymphoma, Stage IV Anaplastic Large Cell Lymphoma City of Hope Medical Center April 13, 2017
NCT03233347 Recruiting Ann Arbor Stage I Hodgkin Lymphoma, Ann Arbor Stage IA Hodgkin Lymphoma, Ann Arbor Stage IB Hodgkin Lymphoma, Ann Arbor Stage II Hodgkin Lymphoma, Ann Arbor Stage IIA Hodgkin Lymphoma, Ann Arbor Stage IIB Hodgkin Lymphoma Academic and Community Cancer Research United July 28, 2017
NCT02166463 Recruiting Ann Arbor Stage IIB Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IV Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma, Ann Arbor Stage IVB Hodgkin Lymphoma, Childhood Hodgkin Lymphoma, Classic Hodgkin Lymphoma National Cancer Institute (NCI) June 18, 2014
NCT02292979 Active, not recruiting Hodgkin Lymphoma The Lymphoma Academic Research Organisation November 18, 2014
NCT02243436 Active, not recruiting CLASSICAL HODGKIN LYMPHOMA Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea September 18, 2014
NCT01920932 Active, not recruiting Stage II Childhood Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma St. Jude Children's Research Hospital August 12, 2013
NCT03246750 Not yet recruiting Extranodal NK/T-cell Lymphoma The Thai Lymphoma Study Group August 11, 2017
NCT01868451 Recruiting Hodgkin Lymphoma Memorial Sloan Kettering Cancer Center June 4, 2013
NCT03540849 Recruiting Hodgkin Lymphoma University Hospital, Caen May 30, 2018
NCT03576378 Active, not recruiting Hodgkin Lymphoma Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea July 3, 2018
NCT03527628 Recruiting Classical Hodgkin Lymphoma, Hodgkin Lymphoma (Category), Hodgkin Disease, Hodgkin Lymphoma King Abdullah International Medical Research Center May 17, 2018
NCT02098512 Recruiting Hodgkin Lymphoma New York Medical College March 28, 2014
NCT01712490 Active, not recruiting Hodgkin Lymphoma Millennium Pharmaceuticals, Inc. October 23, 2012
NCT02398240 Recruiting Hodgkin Lymphoma Mitchell Cairo March 25, 2015
NCT03517137 Not yet recruiting Advanced Hodgkin Lymphoma European Organisation for Research and Treatment of Cancer - EORTC May 7, 2018
NCT03719105 Recruiting NK-Cell Lymphoma, NK-Cell Leukemia, Peripheral T Cell Lymphoma New York Medical College October 25, 2018
NCT03755804 Recruiting Hodgkin Lymphoma St. Jude Children's Research Hospital November 28, 2018
NCT02453594 Active, not recruiting Hodgkin Lymphoma Merck Sharp & Dohme Corp. May 25, 2015
NCT02661503 Recruiting Classical Hodgkin Lymphoma University of Cologne January 22, 2016
NCT03703050 Recruiting Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma Gustave Roussy, Cancer Campus, Grand Paris October 11, 2018
NCT03049449 Recruiting Lymphoma, Large-Cell, Anaplasitc, Hodgkin Disease, Lymphoma, Hodgkins, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Extranodal NK-T-Cell National Cancer Institute (NCI) February 10, 2017
NCT03766516 Recruiting Relapsed or Refractory Anaplastic Large Cell Lymphoma & Hodgkin Lymphoma Samsung Medical Center December 6, 2018
NCT01476839 Recruiting Recurrent Adult Hodgkin Lymphoma City of Hope Medical Center November 22, 2011

Table 2. Approved Drugs of Brentuximab vedotin**

INN (trade name) Therapeutic area Dose Strength Route Company Marketing start Market
Adcetris Hodgkin Lymphoma, Systemic Anaplastic Large Cell Lymphoma Concentrate for injection 50MG / vial Intravenous infusion Seattle Genetics, Inc. August 19, 2011 Ranibizumab Overview
Adcetris Lymphoma, Non-Hodgkin; Hodgkin Disease Concentrate for injection 50MG / vial Intravenous infusion Takeda Pharma A/S October 25, 2012 Ranibizumab Overview

What We Provide

Therapeutic Antibody

We provide high-quality for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
*The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Brentuximab+vedotin

**Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125388

Send Inquiry

  • Verification code
    Click image to refresh the verification code.
© 2007 - 2019 Creative BioLabs All Rights Reserved
  • 0
  • 0

Cart