Identification
- Summary
Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager used to treat unresectable or metastatic uveal melanoma.
- Brand Names
- Kimmtrak
- Generic Name
- Tebentafusp
- DrugBank Accession Number
- DB15283
- Background
Tebentafusp is a gp100 peptide-HLA-directed CD3 T cell engager.5 It is a bispecific, fusion protein and first-in-class drug of immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs), a recently developed cancer immunotherapy with a novel mechanism of action. ImmTACs bind to target cancer cells that express a specific antigen of interest and recruit cytotoxic T cells to lyse the cells, such as melanocytes.1,2
Uveal melanoma is a rare ocular tumour with often poor prognosis and limited treatment options. Even after surgical ablation or removal of the ocular tumour, almost 50% of patients with uveal melanoma develop metastatic disease.1 On January 26, 2022, tebentafusp was first approved by the FDA for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma. This approval marks the first bispecific T cell engager to be approved by the FDA to treat a solid tumour and being the first and only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA.5 Tebentafusp was subsequently approved for the same indication in the EU in April 2022.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Synonyms
- Tebentafusp
- External IDs
- IMCGP100
Pharmacology
- Indication
Tebentafusp is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic uveal melanoma (um) •••••••••••• ••••• •••••••••• •••••••• ••••• ••••••• ••••••••• Treatment of Unresectable uveal melanoma •••••••••••• ••••• •••••••••• •••••••• ••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
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Tebentafusp is novel immunotherapy that causes cytotoxicity of cancer cells. Tebentafusp increased the serum levels of cytokines (IFN-γ, TNFα, IL-2, IL-6, IL-10 and IL-1RA) and chemokines (CXCL9, CXCL10, CXCL11, hepatocyte growth factor, and monocyte chemoattractant protein-1) during the first three doses. The levels of cytokines and chemokines peaked between eight to 24 hours after treatment, and levels returned to baseline before subsequent doses. In subsequent treatment cycles, cytokine elevation occurred in fewer patients with lesser intensity than the first three doses. Tebentafusp also reduced lymphocyte counts after the first three doses, which returned to baseline before subsequent doses.4 In phase III clinical trials, patients treated with tebentafusp showed a better overall survival rate compared to pembrolizumab, ipilimumab, or dacarbazine.5
- Mechanism of action
Glycoprotein 100 (gp100) is a transmembrane glycoprotein highly expressed in melanoma cells and weakly expressed by normal melanocytes or other tissues. Gp100 is presented as a human leukocyte antigen (HLA)-peptide complex on the cell surface. Gp100 has a particularly high affinity for the HLA-A subtype HLA-A*02:01.1,2 HLAs are part of a protein complex that normally regulates immune function: natural T cell responses are initiated by the interaction between the T-cell receptor (TCR) and its peptide antigen, such as gp100, presented by HLA on the surface of a target cell.3
Tebentafusp is a bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor CD3 T cell engager. It consists of a TCR targeting domain - or a TCR arm - fused to a single-chain variable fragment (scFv) anti-CD3 effector domain.1 The TCR arm binds to a gp100 peptide bound to HLA-A on the uveal melanoma tumour cell surface. The anti-CD3 effector domain of tebentafusp engages and activates CD3+ T cells to inflammatory cytokines and cytolytic proteins, which results in direct lysis of uveal melanoma tumour cells.4 The anti-CD3 fragment of the drug has a lower affinity, so the T cells are not stimulated unless tebentafusp has detected gp100.2
Tebentafusp is only effective in HLA-A*02:01-positive patients.4,2
Target Actions Organism AMelanocyte protein PMEL binderHumans - Absorption
After a single dose administration, Cmax and AUC0-7d increased dose-proportionally from 20 to 68 mg (0.3 to 1 times the approved recommended dose). Following administration of the approved recommended dosage in patients with metastatic uveal melanoma, the steady-state geometric mean (% CV) Cmax of tebentafusp was 13 ng/mL (34.6%) and AUC0-7d was 4.6 ng.day/mL (23%) with no accumulation.4
- Volume of distribution
The geometric mean (%CV) steady-state volume of distribution is 7.56 L (24%).4
- Protein binding
There is no information available.
- Metabolism
Tebentafusp is expected to be catabolized into small peptides and amino acids.4
- Route of elimination
There is no information available.
- Half-life
The median terminal half-life is 7.5 hours, with a range of 6.8 to 7.5 hours.4
- Clearance
The geometric mean clearance (%CV) of tebentafusp is 16.4 L/d (24.5%).4
- Adverse Effects
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There is limited information regarding the LD50 and overdose of tebentafusp.
- 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 softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Tebentafusp is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Tebentafusp is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Tebentafusp is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Tebentafusp is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Tebentafusp is combined with Bupivacaine. - 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 Kimmtrak Injection, solution, concentrate 100 mcg/0.5mL Intravenous Immunocore Ireland Limited 2022-05-04 Not applicable EU 
Kimmtrak Solution 100 mcg / 0.5 mL Intravenous Immunocore Ireland Limited 2022-08-23 Not applicable Canada 
Kimmtrak Injection, solution, concentrate 100 ug/0.5mL Intravenous Immunocore Commercial LLC 2022-01-26 Not applicable US 
Categories
- ATC Codes
- L01XX75 — Tebentafusp
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- N658GY6L3E
- CAS number
- 1874157-95-5
References
- General References
- Damato BE, Dukes J, Goodall H, Carvajal RD: Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma. Cancers (Basel). 2019 Jul 11;11(7). pii: cancers11070971. doi: 10.3390/cancers11070971. [Article]
- Martinez-Perez D, Vinal D, Solares I, Espinosa E, Feliu J: Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. Cancers (Basel). 2021 Nov 27;13(23). pii: cancers13235968. doi: 10.3390/cancers13235968. [Article]
- Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, Evans TRJ, Anthoney A, Shoushtari AN, Hamid O, Gupta A, Vardeu A, Leach E, Naidoo R, Stanhope S, Lewis S, Hurst J, O'Kelly I, Sznol M: Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Clin Cancer Res. 2020 Nov 15;26(22):5869-5878. doi: 10.1158/1078-0432.CCR-20-1247. Epub 2020 Aug 18. [Article]
- FDA Approved Drug Products: KIMMTRAK (tebentafusp-tebn) injection, for intravenous use [Link]
- BioSpace News: Immunocore announces FDA approval of KIMMTRAK® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma [Link]
- NIH NCATS Inxight Drugs: TEBENTAFUSP [Link]
- EMA Summary of Product Characteristics: Kimmtrak (tebentafusp) concentrate for intravenous infusion [Link]
- External Links
- 2590743
- Wikipedia
- Immunocore
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Not Yet Recruiting Treatment Uveal Melanoma 1 2 Active Not Recruiting Treatment Uveal Melanoma 1 2 Not Yet Recruiting Treatment Uveal Melanoma 1 2 Recruiting Diagnostic Melanoma / Uveal Melanoma 1 2 Terminated Treatment Malignant Melanoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 100 mcg/0.5mL Injection, solution, concentrate Intravenous 100 ug/0.5mL Solution Intravenous 100 mcg / 0.5 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.
- Specific Function
- Identical protein binding
- Gene Name
- PMEL
- Uniprot ID
- P40967
- Uniprot Name
- Melanocyte protein PMEL
- Molecular Weight
- 70254.63 Da
References
- Damato BE, Dukes J, Goodall H, Carvajal RD: Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma. Cancers (Basel). 2019 Jul 11;11(7). pii: cancers11070971. doi: 10.3390/cancers11070971. [Article]
- Martinez-Perez D, Vinal D, Solares I, Espinosa E, Feliu J: Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. Cancers (Basel). 2021 Nov 27;13(23). pii: cancers13235968. doi: 10.3390/cancers13235968. [Article]
- Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, Evans TRJ, Anthoney A, Shoushtari AN, Hamid O, Gupta A, Vardeu A, Leach E, Naidoo R, Stanhope S, Lewis S, Hurst J, O'Kelly I, Sznol M: Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Clin Cancer Res. 2020 Nov 15;26(22):5869-5878. doi: 10.1158/1078-0432.CCR-20-1247. Epub 2020 Aug 18. [Article]
- FDA Approved Drug Products: KIMMTRAK (tebentafusp-tebn) injection, for intravenous use [Link]
Drug created at May 20, 2019 15:08 / Updated at April 22, 2024 18:20