Glofitamab
Identification
- Summary
Glofitamab is a bispecific monoclonal antibody directed against CD20 and CD3 which is used for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
- Generic Name
- Glofitamab
- DrugBank Accession Number
- DB16371
- Background
Glofitamab is a full-length bispecific monoclonal antibody with affinity for both CD20 and CD3 surface antigens found on B- and T-cells, respectively. It has a 2:1 configuration, with bivalency towards CD20 and monovalency towards CD3, and works by recruiting T-cells directly to the surface of cancerous B-cells.3,2
Glofitamab was approved by Health Canada in March 2023 for the treatment of certain patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), becoming the first CD20/CD3 bispecific monoclonal antibody approved for DLBCL.5 The most common type of non-Hodgkin lymphoma,4 DLBCL is relatively sensitive to chemotherapy and generally responsive to first-line treatment regimens like CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)4 - despite this, as many as 40% of patients will experience relapsed or refractory disease.5,1 In the context of relapsed or refractory DLBCL, glofitamab provides an alternative treatment option for patients having failed other systemic therapies or for whom targeted therapies - such as CAR-T cell therapy - are inappropriate.
In June 2023, the FDA approved the use of glofitamab for the treatment of patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy under accelerated approval based on response rate and durability of response.6,7
Glofitamab was granted conditional marketing authorization in July 2023 by the EMA for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. This approval is based on the positive results obtained from the phase I/II NP30179 study, where 35.2% of study participants achieved a complete response.9
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 194000.0 Da (Peptide chains only, without heavy chain C terminal lysine residues, with N terminal glutamines converted into pyroglutamates due to cyclization)
- Sequences
>SUBUNIT_1 QVQLVQSGAEVKKPGSSVKVSCKASGYAFSYSWINWVRQAPGQGLEWMGRIFPGDGDTDY NGKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCARNVFDGYWLVYWGQGTLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVEDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDEKVEPKSCDGGGGSGGGGSQAVVTQE PSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIGGTNKRAPGTPARFSGS LLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFGGGTKLTVLSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPGK
>SUBUNIT_2 QVQLVQSGAEVKKPGSSVKVSCKASGYAFSYSWINWVRQAPGQGLEWMGRIFPGDGDTDY NGKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCARNVFDGYWLVYWGQGTLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVEDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDEKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVCTLPPSRDEL TKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>SUBUNIT_3 DIVMTQTPLSLPVTPGEPASISCRSSKSLLHSNGITYLYWYLQKPGQSPQLLIYQMSNLV SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQNLELPYTFGGGTKVEIKRTVAAPSV FIFPPSDRKLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4 DIVMTQTPLSLPVTPGEPASISCRSSKSLLHSNGITYLYWYLQKPGQSPQLLIYQMSNLV SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQNLELPYTFGGGTKVEIKRTVAAPSV FIFPPSDRKLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_5 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYAT YYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAYWGQGTL VTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- NIH Inxight: Glofitamab [Link]
- Synonyms
- Anti-CD20/CD3 bispecific monoclonal antibody RO7082859
- Glofitamab
- External IDs
- RG-6026
- RG6026
- RO-7082859
- RO7082859
- WHO 11145
Pharmacology
- Indication
Glofitamab is indicated in Canada for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy. This indication has been authorized pending the results of trials designed to verify glofitamab's clinical benefit.3
The FDA approved glofitamab under accelerated approval for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.7
Glofitamab was also approved by the EMA to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy.8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Diffuse large b-cell lymphoma (dlbcl) •••••••••••• ••••• ••••• •• ••••• •• •••••••• •••••••• •••••••••• ••• ••••• •••• ••••••• •••••••••• ••••••••• ••••••••••• Treatment of Large b cell lymphoma •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• ••••••••• Treatment of Primary mediastinal (thymic) large b cell lymphoma (pmbcl) •••••••••••• ••••• •••••••••• ••• ••••• •••• •••••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• ••••••••• ••••••••••• Treatment of Refractory diffuse large b cell lymphoma (dlbcl) •••••••••••• ••••• •••••••••• ••• ••••• •••• •••••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• ••••••••• ••••••••••• Treatment of Refractory diffuse large b-cell lymphoma, not otherwise specified •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
In clinical trials, 10/152 patients exposed to glofitamab experienced a prolonged QTc interval (post-baseline QTc >450 ms), although only one of these cases was determined to be clinically significant and no patients were required to discontinue treatment due to QTc prolongation.3
Glofitamab can cause cytokine release syndrome (CRS) which may be serious or life-threatening in some patients.3 To limit the risk of CRS, prescribing information states that all patients must receive pre-treatment with obinutuzumab seven days prior to beginning treatment with glofitamab. In addition, patients should be well-hydrated and should receive a premedication regimen comprising a glucocorticoid, analgesic/antipyretic, and/or antihistamine, dependent on the patient and the cycle.3 The dose of glofitamab should be titrated gradually and according to prescribing information to further limit the risk of CRS, and patients should be monitored for 10 hours following the first infusion and as required thereafter.
- Mechanism of action
Glofitamab is a bispecific monoclonal antibody targeted towards CD20 surface antigens - found on B-cells - and CD3 protein complexes found on the surface of T-cells.3 It binds bivalently to CD20 and monovalently to CD3, thereby creating an immunological synapse that serves to recruit T-cells to CD20-expressing B-cells. This simultaneous binding allows for potent T-cell activation and proliferation which ultimately results in the lysis of the target B-cells.3
Target Actions Organism AB-lymphocyte antigen CD20 binderantibodyHumans AT-cell surface glycoprotein CD3 binderantibodyHumans - Absorption
According to population pharmacokinetic analysis, the geometric mean Cmax of glofitamab on day 1 after the first infusion of 2.5 mg was 0.674 µg/mL. At the end of cycle 2 - following the step-up dosing to a final dose of 30 mg - the geometric mean Cmax was estimated via population pharmacokinetic modeling to be 7.67 µg/mL.3
Non-compartmental analysis following a single dose of 10 mg showed a geometric mean Cmax of 2.34 µg/mL, Tmax of 8.05, and AUCinf of 244 hr*µg/mL.3
- Volume of distribution
Following intravenous administration, population pharmacokinetic modeling estimated the central and peripheral volumes of distribution to be 3.33 L and 2.18 L, respectively, with an intercompartmental clearance of 0.674 L/day.3
- Protein binding
Not Available
- Metabolism
The metabolism of glofitamab has not been directly studied. As with other therapeutic antibodies, it is likely metabolized primarily via catabolism to smaller peptides and amino acids.3
- Route of elimination
Not Available
- Half-life
The transition from non-linear to linear clearance phase was estimated to take approximately 1.56 days, after which the effective linear half-life of glofitamab is approximately 6.54 days.3
- Clearance
Glofitamab's serum concentration-time data are best described by a two-compartment model and both time-independent and time-varying clearance parameters. Population pharmacokinetic modeling estimated a time-independent clearance parameter of 0.602 L/day, and an initial time-varying clearance parameter of 0.396 L/day.3
- Adverse Effects
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- Toxicity
There was no experience with overdosage of glofitamab in clinical trials.3
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Glofitamab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Glofitamab. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Glofitamab. Abiraterone The serum concentration of Abiraterone can be increased when it is combined with Glofitamab. Abrocitinib The serum concentration of Abrocitinib can be increased when it is combined with Glofitamab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Columvi Solution 2.5 mg / 2.5 mL Intravenous Hoffmann La Roche 2023-07-05 Not applicable Canada Columvi Injection, solution, concentrate 10 mg Intravenous Roche Registration Gmb H 2023-07-22 Not applicable EU Columvi Solution 10 mg / 10 mL Intravenous Hoffmann La Roche 2023-07-05 Not applicable Canada Columvi Injection, solution, concentrate 2.5 mg Intravenous Roche Registration Gmb H 2023-07-22 Not applicable EU Columvi Concentrate 10 mg/10mL Intravenous Genentech, Inc. 2023-06-15 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 06P3KLK2J8
- CAS number
- 2229047-91-8
References
- General References
- Wang C, Liu Y: Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. J Hematol Oncol. 2023 Mar 10;16(1):20. doi: 10.1186/s13045-023-01420-w. [Article]
- Gonzalez Barca E: Role of Bispecific Antibodies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma in the CART Era. Front Immunol. 2022 Jul 19;13:909008. doi: 10.3389/fimmu.2022.909008. eCollection 2022. [Article]
- Health Canada Product Monograph: Columvi (glofitamab) concentrate for solution for intravenous infusion [Link]
- Canadian Cancer Society: Diffuse large B-cell lymphoma [Link]
- BioSpace: COLUMVI® (Glofitamab for Injection) Receives Health Canada Authorization with Conditions for Adult Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma [Link]
- Globe News Wire: FDA approves Roche’s Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma [Link]
- FDA Approved Drug Products: COLUMVI (glofitamab-gxbm) injection for intravenous use (June 2023) [Link]
- EMA Approved Drug Products: Columvi (glofitamab) injection, for intravenous use [Link]
- European Commission approves Roche's fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma [Link]
- External Links
- 2639782
- Wikipedia
- Glofitamab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Recruiting Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1 3 Recruiting Treatment Large B Cell Lymphoma 1 3 Recruiting Treatment Lymphoma 1 2 Active Not Recruiting Treatment Refractory Diffuse Large B Cell Lymphoma (DLBCL) / Refractory Indolent Adult Non-Hodgkin Lymphoma / Refractory Mantle Cell Lymphoma / Refractory Primary Mediastinal Large B-Cell Cell Lymphoma / Refractory Transformed B-cell Non-Hodgkin Lymphoma 1 2 Not Yet Recruiting Other Diffuse Large B-Cell Lymphoma (DLBCL) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Concentrate Intravenous 10 mg/10mL Injection, solution, concentrate Intravenous 10 mg Injection, solution, concentrate Intravenous 2.5 mg Solution Intravenous 10 mg / 10 mL Solution Intravenous 2.5 mg / 2.5 mL Solution, concentrate Intravenous 2.5 mg/2.5mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderAntibody
- General Function
- Mhc class ii protein complex binding
- Specific Function
- This protein may be involved in the regulation of B-cell activation and proliferation.
- Gene Name
- MS4A1
- Uniprot ID
- P11836
- Uniprot Name
- B-lymphocyte antigen CD20
- Molecular Weight
- 33076.99 Da
References
- Health Canada Product Monograph: Columvi (glofitamab) concentrate for solution for intravenous infusion [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderAntibody
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- The CD3 complex mediates signal transduction.
Components:
References
- Health Canada Product Monograph: Columvi (glofitamab) concentrate for solution for intravenous infusion [Link]
Drug created at December 21, 2020 19:33 / Updated at July 25, 2023 16:37