NAV

Teclistamab

Identification

Summary

Teclistamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T cell engager used to treat relapsed and refractory multiple myeloma in adults as monotherapy.

Brand Names
Tecvayli
Generic Name
Teclistamab
DrugBank Accession Number
DB16655
Background

Teclistamab is an IgG4-PAA bispecific antibody that targets the CD3 receptor expressed on the surface of T cells and B cell maturation antigen (BCMA) expressed on malignant multiple myeloma cells.1 Teclistamab consists of an anti-BCMA arm and an anti-CD3 arm connected via two interchain disulfide bonds,1,7 allowing the drug to recruit CD3-expressing T cells to BCMA-expressing cells to promote T cell–mediated cytotoxicity.1

On August 24, 2022, the European Commission (EC) granted conditional marketing authorization of teclistamab as first-in-class bispecific antibody for the treatment of multiple myeloma, marking its first global approval.5 Teclistamab was later granted accelerated approval by the FDA on October 25, 2022.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6383H9847N1695O2003S40
Protein Average Weight
146000.0 Da (approximate)
Sequences
>anti-BCMA heavy chain
QLQLQESGPGLVKPSETLSLTCTVSGGSISSGSYFWGWIRQPPGKGLEWIGSIYYSGITY
YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHDGAVAGLFDYWGQGTLVTVS
SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE
GNVFSCSVMHEALHNHYTQKSLSLSLGK
>anti-BCMA light chain
SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQPPGQAPVVVVYDDSDRPSGIPER
FSGSNSGNTATLTISRVEAGDEAVYYCQVWDSSSDHVVFGGGTKLTVLGQPKAAPSVTLF
PPSSEELQANKATLVCLISDFYPGAVTVAWKGDSSPVKAGVETTTPSKQSNNKYAASSYL
SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
>anti-CD3 heavy chain
EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYAT
YYAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTL
VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAA
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ
FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKS
RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>anti-CD3 light chain
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPGT
PARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGQPKAAPSVTL
FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY
LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
References:
  1. KEGG DRUG: Teclistamab [Link]
Download FASTA Format
Synonyms
  • Teclistamab
  • Teclistamab-cqyv
External IDs
  • JNJ 64007957
  • JNJ-64007957
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Pharmacology

Indication

Teclistamab is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.4,7

Teclistamab is approved by the EC and FDA under conditional marketing authorization and accelerated approval, respectively. New evidence for this drug will be continuously monitored and reviewed, which will affect continued approval for the drug's indication.

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

Teclistamab promotes T cell-mediated cytotoxicity against BCMA-expressing myeloma cells.1 It works to activate and redistribute T cells. Teclistamab treatment was associated with reduced B-cells and increased concentrations of serum cytokines, including IL-6, IL-10, and IL-2R.4,7

The soluble form of BCMA, which is produced through cleavage at the transmembrane domain by γ-secretase, in patients with multiple myeloma often correlates with disease progression and shorter overall survival rate.1 The majority of patients who received teclistamab had a reduction in soluble BCMA within one month of drug treatment.7

Mechanism of action

B-cell maturation antigen (BCMA) is a member of the tumour necrosis factor family of receptors 1 expressed on the surface of B-lineage cells, as well as late-stage B cells and plasma cells.4,7 BCMA interacts with its ligands to activate survival signalling pathways such as NF-kappa B, STAT3, ERK1/2, and AKT/PI3K,2 and upregulates anti-apoptotic proteins to regulate B-cell maturation, proliferation, and survival.1 Besides B cells, BCMA is also widely expressed on multiple myeloma (MM) cells and supports the survival of MM cells, making it a promising therapeutic target for therapeutic agents for MM.1,2,3

Teclistamab is a bispecific T cell engaging antibody that targets the CD3 receptor, which is expressed on the surface of T cells, and BCMA, which is expressed on malignant cells. Due to its dual binding sites, teclistamab is able to draw CD3+ T cells in close proximity to BCMA+ cells, resulting in T cell activation and T cell-mediated cytotoxicity, which is mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells.4 This effect occurs without regard to T cell receptor specificity or reliance on major histocompatibility complex (MHC) Class 1 molecules on the surface of antigen presenting cells.4 Ultimately, teclistamab promotes the lysis and death of BCMA+ cells.4,7

TargetActionsOrganism
AT-cell surface glycoprotein CD3
antibody
Humans
ATumor necrosis factor receptor superfamily member 17
antibody
Humans
Absorption

The mean bioavailability following subcutaneous administration ranges from 69% to 72%.4,7

A study involved patients with multiple myeloma who received step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by a subcutaneous dose of 1.5 mg/kg teclistamab once weekly. The mean accumulation ratio between the first and thirteenth weekly treatment dose of 1.5 mg/kg teclistamab was 4.2-fold for Cmax, 4.1-fold for Ctrough, and 5.3-fold for AUCtau. The mean (CV%) Cmax after administration of 1.5 mg/kg teclistamab was 23.8 mcg/mL (55%). The median (range) Tmax of teclistamab after the first and thirteenth treatment doses were 139 (19 to 168) hours and 72 (24 to 168) hours, respectively. Most subjects who received a dosage range of 0.08 mg/kg to 3 mg/kg teclistamab reached steady-state exposure after 12 weekly treatment doses.7

Volume of distribution

The mean (CV%) volume of distribution of teclistamab was 5.63 L (29%). The volume of distribution of teclistamab increases with increasing body weight.7

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Based on non-compartmental analysis, the mean half-life (SD) was 3.8 (1.7) days (individual values ranging up to 8.8 days) following the first treatment intravenous dose of teclistamab.4

Clearance

Teclistamab exhibits both time-independent and time-dependent clearance.4 The clearance of teclistamab increases with increasing body weight.7

In a study involving patients receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by a subcutaneous dose of 1.5 mg/kg teclistamab once weekly, the geometric mean (CV%) clearance is 0.472 L/day (64%) at the thirteenth dose. The mean (CV%) maximal reduction from baseline to the thirteenth treatment dose was 40.8% (56%). Patients who discontinue teclistamab-cqyv after the 13th treatment dose are expected to have a 50% reduction from Cmax in teclistamab-cqyv concentration at a median (5th to 95th percentile) time of 15 (7 to 33) days after Tmax and a 97% reduction from Cmax in teclistamab-cqyv concentration at a median time of 69 (32 to 163) days after Tmax.7

Adverse Effects
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Toxicity

There is no information regarding acute toxicity of teclistamab. The maximum tolerated dose of teclistamab has not been determined. In clinical studies, doses of up to 6 mg/kg have been administered. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted immediately.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
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ImlifidaseThe therapeutic efficacy of Teclistamab can be decreased when used in combination with Imlifidase.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TecvayliSolution153 mg / 1.7 mLSubcutaneousJanssen Pharmaceuticals2023-10-20Not applicableCanada flag
TecvayliInjection10 mg/1mLSubcutaneousJanssen Biotech, Inc.2022-10-25Not applicableUS flag
TecvayliInjection, solution90 mg/mlSubcutaneousJanssen Cilag International Nv2023-02-08Not applicableEU flag
TecvayliSolution30 mg / 3 mLSubcutaneousJanssen Pharmaceuticals2023-10-20Not applicableCanada flag
TecvayliInjection, solution10 mg/mlSubcutaneousJanssen Cilag International Nv2023-02-08Not 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
54534MX6Z9
CAS number
2119595-80-9

References

General References
  1. Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
  2. Wu L, Huang Y, Sienkiewicz J, Sun J, Guiang L, Li F, Yang L, Golubovskaya V: Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Cancers (Basel). 2022 May 20;14(10). pii: cancers14102518. doi: 10.3390/cancers14102518. [Article]
  3. Cho SF, Anderson KC, Tai YT: Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. Front Immunol. 2018 Aug 10;9:1821. doi: 10.3389/fimmu.2018.01821. eCollection 2018. [Article]
  4. EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]
  5. Johnson & Johnson: Janssen Marks First Approval Worldwide for TECVAYLI® (teclistamab) with EC Authorisation of First-in-Class Bispecific Antibody for the Treatment of Patients with Multiple Myeloma [Link]
  6. FDA: FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma [Link]
  7. FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
RxNav
2619426
Wikipedia
Teclistamab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Refractory Cancer / Relapsed Cancer1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentMultiple Myeloma (MM)2
3RecruitingTreatmentRelapsed/Refractory Multiple Myeloma (RRMM)2
2Active Not RecruitingTreatmentHematological Malignancy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous10 mg/1mL
InjectionSubcutaneous90 mg/1mL
Injection, solutionSubcutaneous10 mg/ml
Injection, solutionSubcutaneous90 mg/ml
SolutionSubcutaneous153 mg / 1.7 mL
SolutionSubcutaneous30 mg / 3 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, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
  2. FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
  3. EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]
Details2. Tumor necrosis factor receptor superfamily member 17
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.
Specific Function
Signaling receptor activity
Gene Name
TNFRSF17
Uniprot ID
Q02223
Uniprot Name
Tumor necrosis factor receptor superfamily member 17
Molecular Weight
20165.065 Da
References
  1. Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
  2. FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
  3. EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]

Drug created at March 24, 2021 23:14 / Updated at September 12, 2023 18:32