NAV

Epcoritamab

Identification

Summary

Epcoritamab is a bispecific CD20-directed CD3 T-cell engager used to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults.

Brand Names
Epkinly
Generic Name
Epcoritamab
DrugBank Accession Number
DB16672
Background

Epcoritamab is an IgG1-bispecific antibody that simultaneously binds to CD3 on T-cells and CD20 on B-cells.1,2,3,4 Epcoritamab promotes the activation and expansion of T-cells and, by being able to bind to both CD20 and CD3, it leads to the T-cell–mediated killing of CD20+ malignant B cells.3,4 Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of cancer commonly treated with several cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Although this regimen is effective in up to 60% of patients, patients with relapsed or refractory DLBCL have poor outcomes.1,2 The use of epcoritamab in this group of patients has high response rates, durable complete responses and manageable adverse events with few discontinuations.1

The use of epcoritamab may lead to cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.4 It is administered subcutaneously and is currently being evaluated as a monotherapy and in combination for the treatment of a variety of hematologic malignancies. In May 2023, epcoritamab was approved by the FDA under accelerated approval for the treatment of relapsed or refractory DLBCL. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).4,5 In September 2023, epcoritamab was also approved in the EU for the same indication.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6471H9999N1735O2007S44
Protein Average Weight
149000.0 Da (approximate)
Sequences
>A chain_anti-CD3E
EVKLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYAT
YYADSVKDRFTISRDDSKSSLYLQMNNLKTEDTAMYYCVRHGNFGNSYVSWFAYWGQGTL
VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAP
EFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPR
EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
>B chain_anti-CD20
EVQLVESGGGLVQPDRSLRLSCAASGFTFHDYAMHWVRQAPGKGLEWVSTISWNSGTIGY
ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFE
GGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
>C chain_anti-CD3E
QAVVTQEPSFSVSPGGTVTLTCRSSTGAVTTSNYANWVQQTPGQAFRGLIGGTNKRAPGV
PARFSGSLIGDKAALTITGAQADDESIYFCALWYSNLWVFGGGTKLTVLGQPKAAPSVTL
FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY
LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
>D chain_anti-CD20
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG: Epcoritamab (D12368) [Link]
  2. WHO: International Nonproprietary Names for Pharmaceutical Substances (INN) [Link]
Download FASTA Format
Synonyms
  • Epcoritamab-bysp
External IDs
  • GEN-3013
  • GEN3013
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Pharmacology

Indication

Epcoritamab is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.4,6 This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory diffuse large b cell lymphoma (dlbcl)••••••••••••••••••••••••••
Treatment ofRelapsed diffuse large b-cell lymphoma (dlbcl)••••••••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

The use of epcoritamab may lead to low levels of circulating B-cells. After the recommended dose of epcoritamab was administered to patients with detectable B-cell levels after the first full dose of 48 mg, circulating B-cells decreased to undetectable levels and remained depleted for the rest of the treatment. Epcoritamab at doses equal to and greater than 0.04 mg may also cause a transient elevation of circulating cytokines, including IL-2, IL-6, IL-10, TNF-α, and IFN-γ. After the first dose of epcoritamab on cycle 1 day 1, cytokine levels increased within 24 hours and reached maximum levels after the first 48 mg dose on cycle 1 day 15. Cytokine levels returned to baseline before the next 48 mg full dose on cycle 1 day 22.4

The use of epcoritamab can cause cytokine release syndrome as well as life-threatening and fatal immune effector cell-associated neurotoxicity syndrome. It may also cause infections, cytopenias and embryo-fetal toxicity.4

Mechanism of action

Epcoritamab is a humanized bispecific IgG1 antibody that targets CD20 on B-cells and CD3 on T-cells. Unlike other monoclonal antibodies that target a single receptor on the surface of lymphocytes, epcoritamab can recognize and bind two different targets, the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and healthy B-lineage cells. By targeting both receptors, epcoritamab promotes the release of proinflammatory cytokines and the lysis of CD20+ malignant B-cells through selective T-cell–mediated cytotoxic activity.1,4

TargetActionsOrganism
AB-lymphocyte antigen CD20
binder
antibody
Humans
AT-cell surface glycoprotein CD3 epsilon chain
binder
antibody
Humans
Absorption

Over a full dosage range from 1.5 to 60 mg (0.03125 to 1.25 times the recommended dose), the AUC of epcoritamab increases in a more than dose-proportional manner. A Cmax of 11.1 mcg/mL was achieved after the eleventh dose of 48 mg (first dose of cycle 4). After the first full dose, the Tmax of epcoritamab was 4 days, and at the end of the weekly dosing regimen (end of Cycle 3), the Tmax was 2.3 days.4

Volume of distribution

Epcoritamab has an apparent total volume of distribution of 25.6 L.4

Protein binding

Not available.

Metabolism

As a monoclonal antibody, epcoritamab is expected to be metabolized into small peptides by catabolic pathways throughout the body.4

Route of elimination

Since epcoritamab is an immunoglobulin G (IgG) antibody, it is expected to be mainly eliminated via intracellular catabolism.

Half-life

A full dose of epcoritamab (48 mg) has a half-life of approximately 22 days at the end of the third treatment cycle.4

Clearance

A full dose of epcoritamab (48 mg) has an apparent total clearance of approximately 0.53 L/day at the end of the third treatment cycle.4

Adverse Effects
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Toxicity

Toxicity information regarding epcoritamab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.4 Symptomatic and supportive measures are recommended. The carcinogenicity or genotoxicity of epcoritamab has not been evaluated. No dedicated fertility studies have been conducted with epcoritamab.4

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.
DrugInteraction
Integrate drug-drug
interactions in your software
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Epcoritamab.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Epcoritamab.
AbirateroneThe serum concentration of Abiraterone can be increased when it is combined with Epcoritamab.
AbrocitinibThe serum concentration of Abrocitinib can be increased when it is combined with Epcoritamab.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is combined with Epcoritamab.
Food Interactions
No interactions found.

Products

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International/Other Brands
Epkinly (Genmab US, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EpkinlyInjection, solution, concentrate4 mg/0.8mLSubcutaneousGenmab US, Inc.2023-05-19Not applicableUS flag
EpkinlyInjection, solution48 mg/0.8mLSubcutaneousGenmab US, Inc.2023-05-19Not applicableUS flag
EpkinlySolution60 mg / mLSubcutaneousAbbvie2023-12-18Not applicableCanada flag
EpkinlySolution5 mg / mLSubcutaneousAbbvie2023-12-18Not applicableCanada flag
TepkinlyInjection, solution48 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2023-11-28Not applicableEU flag

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
D6OMY2L0WA
CAS number
2134641-34-0

References

Synthesis Reference

Van Der Brink, E., et al. (2019). Humanized or chimeric CD3 antibodies (U.S. Patent No. 10,465,006 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/2d/41/2d/932e259d52f1b3/US10465006.pdf

General References
  1. Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ: Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. doi: 10.1200/JCO.22.01725. Epub 2022 Dec 22. [Article]
  2. 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]
  3. Li T, Hiemstra IH, Chiu C, Oliveri RS, Elliott B, DeMarco D, Salcedo T, Egerod FL, Sasser K, Ahmadi T, Gupta M: Semimechanistic Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B-Cell Lymphomas. Clin Pharmacol Ther. 2022 Nov;112(5):1108-1119. doi: 10.1002/cpt.2729. Epub 2022 Sep 27. [Article]
  4. FDA Approved Drug Products: EPKINLY (epcoritamab-bysp) injection for subcutaneous use (May 2023) [Link]
  5. PR NewsWire: EPKINLY (epcoritamab-bysp) Approved by U.S. FDA as the First and Only Bispecific Antibody to Treat Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [Link]
  6. EMA Summary of Product Characteristics: Tepkinly (epcoritamab) concentrate for solution for subcutaneous injection [Link]
  7. GlobeNewswire: Genmab Announces European Commission Approval of TEPKINLY® (epcoritamab) for Adults with Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL) [Link]
RxNav
2637392
Wikipedia
Epcoritamab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentFollicular Lymphoma ( FL)2
2Not Yet RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL) / DLBCL, Nos Genetic Subtypes / Follicular Large Cell Lymphoma / Follicular Large Cell Lymphoma, Relapsed / High Grade B-Cell Lymphoma, Not Otherwise Specified / High-grade B Cell Lymphoma (HGBCL) / High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements1
2Not Yet RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Not Otherwise Specified / Primary Mediastinal (Thymic) Large B Cell Lymphoma (PMBCL) / Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous48 mg/0.8mL
Injection, solution, concentrateSubcutaneous4 mg/0.8mL
SolutionSubcutaneous5 mg / mL
SolutionSubcutaneous60 mg / mL
Injection, solutionSubcutaneous48 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. B-lymphocyte antigen CD20
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Antibody
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
  1. Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ: Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. doi: 10.1200/JCO.22.01725. Epub 2022 Dec 22. [Article]
  2. FDA Approved Drug Products: EPKINLY (epcoritamab-bysp) injection for subcutaneous use (May 2023) [Link]
Details2. T-cell surface glycoprotein CD3 epsilon chain
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Antibody
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. Required for normal immune responses (PubMed:15546002, PubMed:8490660).
Gene Name
CD3E
Uniprot ID
P07766
Uniprot Name
T-cell surface glycoprotein CD3 epsilon chain
Molecular Weight
23147.09 Da
References
  1. Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ: Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. doi: 10.1200/JCO.22.01725. Epub 2022 Dec 22. [Article]
  2. FDA Approved Drug Products: EPKINLY (epcoritamab-bysp) injection for subcutaneous use (May 2023) [Link]

Drug created at April 01, 2021 20:42 / Updated at January 05, 2024 02:30