NAV

Talquetamab

Identification

Summary

Talquetamab is a bispecific antibody used to treat adults with relapsed or refractory multiple myeloma.

Brand Names
Talvey
Generic Name
Talquetamab
DrugBank Accession Number
DB16678
Background

Talquetamab is a IgG4-PAA bispecific G protein-coupled receptor class C group 5 member D (GPRC5D)-directed CD3 T-cell engager. It consists of two arms - anti-GPRC5D and anti-CD3 arms - linked by two interchain disulfide bonds, each arm comprising a heavy and light chain.3 Talquetamab binds to GPRC5D, a cell surface receptor expressed predominantly on multiple myeloma cells, and CD3 on T cells. It works to recruit CD3-expressing T cells to GPRC5D-expressing multiple myeloma cells to induce T-cell–mediated cytotoxicity.1

The Committee for Medicinal Products for Human Use (CHMP) of the EMA recommended conditional marketing authorization for talquetamab for the treatment of relapsed or refractory multiple myeloma on July 21, 2023.5 Talquetamab was fully approved by the EMA on August 22, 2023.8 On August 9, 2023, talquetamab was granted FDA accelerated approval.4

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6410H9938N1716O2006S45
Protein Average Weight
147000.0 Da (approximate)
Sequences
>Talquetamab anti-CD3 arm heavy chain
EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYAT
YYAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTL
VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAA
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ
FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTSKAKGQPREPQVYTLPPSQE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSR
WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>Talquetamab anti-CD3 arm light chain
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPGT
PARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGQPKAAPSVTL
FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY
LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
>Talquetamab anti-GPRC5D arm heavy chain
QVQLVQSGAEVKKPGASVKVSCKASGYSFTGYTMNWVRQAPGQGLEWMGLINPYNSDTNY
AQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARVALRVALDYWGQGTLVTVSSAS
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV
FSCSVMHEALHNHYTQKSLSLSLGK
>Talquetamab anti-GPRC5D arm light chain
DIQMTQSPSSLSASVGDRVTITCKASQNVATHVGWYQQKPGKAPKRLIYSASYRYSGVPS
RFSGSGSGTEFTLTISNLQPEDFATYYCQQYNRYPYTFGQGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG DRUG: Talquetamab [Link]
  2. Google Patents: US10562968B2 [Link]
Download FASTA Format
Synonyms
  • IMMUNOGLOBULIN G4 (233-PROLINE,239-ALANINE,240-ALANINE,410-LEUCINE,414-LYSINE), ANTI-(HUMAN CD3 ANTIGEN) (HUMAN MONOCLONAL JNJ-63483043 .GAMMA.4-CHAIN), DISULFIDE WITH HUMAN MONOCLONAL JNJ-63483043 .LAMBDA.-CHAIN, (231->224'), (234->227')-BIS(DISULFIDE)
  • IMMUNOGLOBULIN G4-KAPPA/G4-LAMBDA, ANTI-(HOMO SAPIENS GPRC5D (G PROTEIN-COUPLED RECEPTOR CLASS C GROUP 5 MEMBER D)), AND ANTI-(HOMO SAPIENS CD3E (CD3 EPSILON, LEU-4)), HUMANIZED AND CHIMERIC MONOCLONAL ANTIBODY, BISPECIFIC
  • IMMUNOGLOBULIN G4-KAPPA/G4-LAMBDA, ANTI-(HOMO SAPIENS GPRC5D (G PROTEIN-COUPLED RECEPTOR CLASS C GROUP 5 MEMBER D)), AND ANTI-(HOMO SAPIENS CD3E (CD3 EPSILON, LEU-4)), HUMANIZED AND CHIMERIC MONOCLONAL ANTIBODY; BISPECIFIC GAMMA4 HEAVY CHAIN HUMANIZED AN
External IDs
  • JNJ-63483043
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Pharmacology

Indication

In the US, talquetamab is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.3 This is an accelerated approval indication. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, talquetamab is indicated in patients who received at least three prior therapies and have demonstrated disease progression on the last therapy.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory multiple myeloma•••••••••••••••••••••••• ••••••••••• ••••• •••••••• •••••••••• •••••••• •• ••••• ••••• ••••• ••••• •• •••••••• •••••••
Treatment ofRefractory multiple myeloma••••••••••••••••••• ••••• ••••• •• •••••••
Treatment ofRelapsed multiple myeloma•••••••••••••••••••••••• ••••••••••• ••••• •••••••• •••••••••• •••••••• •• ••••• ••••• ••••• ••••• •• •••••••• •••••••
Treatment ofRelapsed multiple myeloma••••••••••••••••••• ••••• ••••• •• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Talquetamab had anti-tumour activity in mouse models of multiple myeloma. It activates T cells, which cause the release of pro-inflammatory cytokines to mediate T-cell–mediated cytotoxicity. Serum concentrations of cytokines (IL-6, IL-10, TNF-α, and IFN-γ) and IL-2R were measured before and after administration of each step-up dose - the first three treatment doses at 0.4 mg/kg once weekly, and the first two treatment doses at 0.8 mg/kg every two weeks. Increased IL-6, IL-10, and IL-2R concentrations were observed during this period. Higher talquetamab exposures (i.e., AUC and Cmax) are associated with a higher incidence of some adverse reactions, including oral toxicity, nail toxicity, and skin reactions. The exposure-response relationships for effectiveness and the time course of the pharmacodynamic response of talquetamab have not been fully characterized.3

Mechanism of action

G protein-coupled receptor class C group 5 member D (GPRC5D) is an orphan G protein-coupled receptor predominantly expressed in cells with a plasma-cell phenotype, including the malignant plasma cells in multiple myeloma (MM).1 This transmembrane receptor protein is often aberrantly expressed in MM cells. In contrast, in normal tissues, it is primarily expressed in epithelial cells that produce hard keratin in the skin and tongue.2,3

Talquetamab is a bispecific T-cell-engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and GPRC5D expressed on the surface of MM cells. It works to recruit CD3-expressing T cells to GPRC5D-expressing MM cells to induce T-cell–mediated cytotoxicity, prevent tumour growth, and promote tumour regression.1 When activated, T cells cause the release of proinflammatory cytokines, promoting the lysis of MM cells.3

TargetActionsOrganism
AT-cell surface glycoprotein CD3
antibody
Humans
AG-protein coupled receptor family C group 5 member D
antibody
Humans
Absorption

The Cmax and AUCtau of talquetamab after subcutaneous administration increased proportionally over a dose range of 0.005 to 0.8 mg/kg weekly (0.01 to 2 times the recommended 0.4 mg/kg weekly treatment dose) and 0.8 to 1.2 mg/kg every two weeks (1 to 1.5 times the recommended 0.8 mg/kg every two weeks treatment dose). Ninety percent of steady-state exposure was achieved 16 weeks after the first treatment dose for both regimens. Following the weekly administration of 0.4 mg/kg, the mean Cmax (coefficient of variation, CV%) was 2940 ng/mL (67%), respectively. Following the biweekly administration of 0.8 mg/kg, the Cmax (CV%) was 3410 ng/mL (63%), respectively.3

The geometric mean (coefficient of variation [CV] %) bioavailability of talquetamab was 59% (22%) when administered subcutaneously. The median (range) Tmax of talquetamab after the first and 17th treatment dose of 0.4 mg/kg weekly were 3.7 (0.9 to 7) days and 2.5 (0.9 to 5.9) days, respectively. The median (range) Tmax of talquetamab after the first and 9th treatment dose of 0.8 mg/kg every two weeks were 3.4 (0.8 to 14) days and 3.6 (1 to 7.7) days, respectively.3

Volume of distribution

The geometric mean (CV%) volume of distribution of talquetamab was 10.1 L (25%).3

Protein binding

No information is available.

Metabolism

Talquetamab is expected to be metabolized into small peptides by catabolic pathways.3

Route of elimination

No information is available.

Half-life

The mean (CV%) terminal half-life was 8.4 (41%) days after the first treatment dose and 12.2 (49%) days at 16 weeks after the first treatment dose.3

Clearance

Talquetamab clearance decreases over time, with a mean (CV%) maximal reduction from the first treatment dose to 16 weeks after the first treatment dose of 40% (56%). The geometric mean (CV%) clearance is 0.90 L/day (63%) at 16 weeks after the first treatment dose.3

Adverse Effects
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Toxicity

There is limited information regarding the acute toxicity and overdosage of talquetamab.

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.
Not Available
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TalveyInjection40 mg/1mLSubcutaneousJanssen Biotech, Inc.2023-08-09Not applicableUS flag
TalveyInjection, solution40 mg/mlSubcutaneousJanssen Cilag International Nv2023-11-28Not applicableEU flag
TalveyInjection3 mg/1.5mLSubcutaneousJanssen Biotech, Inc.2023-08-09Not applicableUS flag
TalveyInjection, solution2 mg/mlSubcutaneousJanssen Cilag International Nv2023-11-28Not 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
Not Available

Chemical Identifiers

UNII
4W3KFI3TN3
CAS number
2226212-40-2

References

General References
  1. Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F: A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342. [Article]
  2. Verkleij CPM, Broekmans MEC, van Duin M, Frerichs KA, Kuiper R, de Jonge AV, Kaiser M, Morgan G, Axel A, Boominathan R, Sendecki J, Wong A, Verona RI, Sonneveld P, Zweegman S, Adams HC, Mutis T, van de Donk NWCJ: Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv. 2021 Apr 27;5(8):2196-2215. doi: 10.1182/bloodadvances.2020003805. [Article]
  3. FDA Approved Drug Products: TALVEY (talquetamab-tgvs) injection, for subcutaneous use [Link]
  4. FDA: FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma [Link]
  5. Johnson & Johnson: Janssen Receives Positive CHMP Opinions for Novel Bispecific Antibodies TALVEY®▼ (talquetamab) and TECVAYLI®▼ (teclistamab) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma [Link]
  6. EMA Summary of Opinion: Talvey (talquetamab) [Link]
  7. EMA Approved Drug Products: Talvey (talquetamab) Subcutaneous Injection [Link]
  8. Johnson & Johnson: European Commission Approves TALVEY®▼ (talquetamab), Janssen’s Novel Bispecific Therapy for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma [Link]
RxNav
2644447
Wikipedia
Talquetamab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentRelapsed/Refractory Multiple Myeloma (RRMM)2
3WithdrawnTreatmentRelapsed/Refractory Multiple Myeloma (RRMM)1
2RecruitingTreatmentHematological Malignancy1
2RecruitingTreatmentHigh-Risk de Novo Multiple Myeloma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous3 mg/1.5mL
InjectionSubcutaneous40 mg/1mL
Injection, solutionSubcutaneous2 mg/ml
Injection, solutionSubcutaneous40 mg/ml
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. T-cell surface glycoprotein CD3 (Protein Group)
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction.
Components:
NameUniProt ID
T-cell surface glycoprotein CD3 delta chainP04234
T-cell surface glycoprotein CD3 epsilon chainP07766
T-cell surface glycoprotein CD3 gamma chainP09693
T-cell surface glycoprotein CD3 zeta chainP20963
References
  1. Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F: A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342. [Article]
  2. FDA Approved Drug Products: TALVEY (talquetamab-tgvs) injection, for subcutaneous use [Link]
Details2. G-protein coupled receptor family C group 5 member D
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Not Available
Specific Function
G protein-coupled receptor activity
Gene Name
GPRC5D
Uniprot ID
Q9NZD1
Uniprot Name
G-protein coupled receptor family C group 5 member D
Molecular Weight
38790.52 Da
References
  1. Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F: A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342. [Article]
  2. FDA Approved Drug Products: TALVEY (talquetamab-tgvs) injection, for subcutaneous use [Link]

Drug created at April 01, 2021 21:53 / Updated at November 30, 2023 01:44