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Identification
- Summary
Tarlatamab is a bispecific monoclonal antibody and T-cell engager targeting delta-like ligand 3 (DLL3) and CD3 to treat extensive-stage small cell lung cancer.
- Brand Names
- Imdelltra
- Generic Name
- Tarlatamab
- DrugBank Accession Number
- DB17256
- Background
Tarlatamab is a first-in-class T-cell engager used to treat extensive-stage small cell lung cancer.4 It is a bispecific monoclonal antibody that targets CD3 expressed on the surface of T-cells and delta-like ligand 3 (DLL3), an inhibitory ligand that suppresses Notch signaling and is highly expressed across various SCLC disease stages and treatment statuses.3,1 Its bispecificity causes T-cell activation, the release of inflammatory cytokines, and lysis at DLL3-expressing cells.3
Tarlatamab-dlle was approved by the FDA in May 2024 for use in patients who have failed previous round of platinum-based chemotherapy,3,4 becoming the first DLL3-targeting bispecific T-cell engager to receive marketing approval.1
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 105000.0 Da
- Sequences
>TARLATAMAB_SUBUNIT_1 QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTNYN PSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTVSSGG GGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRPGQAPRL LIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTFGCGTKLEI KSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGN YPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLW YSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK
Download FASTA FormatReferences:
- NIH Inxight Drugs: Tarlatamab [Link]
- Synonyms
- Immunoglobulin scfv-scfv-scfc, anti-(homo sapiens dll3 (delta-like ligand 3)) and anti-(homo sapiens cd3e (cd3 epsilon, leu-4)), monoclonal antibody single chain (scfv)2-scfc, bispecific
- Tarlatamab
- Tarlatamab-dlle
- External IDs
- AMG-757
- AMG757
Pharmacology
- Indication
Tarlatamab is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.3
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 Extensive-stage small cell lung cancer (sclc) •••••••••••• ••••• ••••••• ••••••••••• •• •• ••••• •••••••••••••• •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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Tarlatamab exerts its pharmacologic effects by selectively recruiting T-cells to cancerous cells expressing DLL3.3
Serious neurologic toxicities have been reported with the use of tarlatamab, including immune effector cell-associated neurotoxicity syndrome (ICANS). There was no observed exposure-response relationship with regards to efficacy over the studied dose range, but there was an increased risk of neurologic toxicity (including ICANS) and neutropenia at higher exposure.3 Tarlatamab may also cause cytokine release syndrome (CRS), most commonly following the first dose, which can be serious or life-threatening.3 Patients should be monitored closely for signs and symptoms suggestive of CRS or neurologic toxicities.
- Mechanism of action
Tarlatamab is a bispecific monoclonal antibody and T-cell engager.3 It is directed at both delta-like ligand 3 (DLL3) expressed on cell surfaces and CD3 expressed on the surface of T-cells. DLL3 is an inhibitory ligand that suppresses Notch signaling which is aberrantly expressed on the surface of up to 85% of SCLC cells and minimally expressed in normal tissues, making it a compelling therapeutic target.2
Tarlatamab serves to recruit and direct T-cells towards tumor cells expressing DLL3, resulting in T-cell activation and the release of inflammatory cytokines ultimately causing lysis of DLL3-expressing cells.3
Target Actions Organism ADelta-like protein 3 binderantibodyHumans AT-cell surface glycoprotein CD3 binderantibodyHumans - Absorption
Tarlatamab is administered intravenously and therefore has an effective bioavailability of 100%.3 Following the first step-up dose of 1 mg, the geometric mean Cavg was 102 ng/mL, the geometric mean Cmax was 285, and the geometric mean Ctrough was 47 ng/mL.3 At steady-state, with the administration of 10 mg every 2 weeks, the geometric mean Cavg was 1040 ng/mL, the geometric mean Cmax was 3400, and the geometric mean Ctrough was 495 ng/mL.3
- Volume of distribution
At steady-state, the volume of distribution of tarlatamab-dlle is 8.6 liters.3
- Protein binding
Not Available
- Metabolism
As with other therapeutic proteins, tarlatamab-dlle is likely metabolized into smaller peptides and amino acids by non-specific catabolic pathways.3
- Route of elimination
Not Available
- Half-life
The median terminal half-life of tarlatamab-dlle is 11.2 days.3
- Clearance
The systemic clearance of tarlatamab-dlle in patients with SCLC is 0.65 L/day.3
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
No data are available regarding overdosage of tarlatamab.
- 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
- Not Available
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 Imdelltra (amg757) Injection, powder, lyophilized, for solution; Kit 2.4 mg/1mg Intravenous AMGEN INC 2024-05-16 Not applicable US 
Imdelltra (amg757) Injection, powder, lyophilized, for solution; Kit 0.9 mg/1mg Intravenous AMGEN INC 2024-05-16 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
Chemical Identifiers
- UNII
- 74X82ST8Q1
- CAS number
- 2307488-83-9
References
- General References
- Su PL, Chakravarthy K, Furuya N, Brownstein J, Yu J, Long M, Carbone D, Li Z, He K: DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy. Mol Cancer. 2024 May 10;23(1):97. doi: 10.1186/s12943-024-02012-z. [Article]
- Addeo A, Banna GL, Friedlaender A: Tarlatamab: a potential new option for recurrent small cell lung cancer. Transl Lung Cancer Res. 2023 Jul 31;12(7):1628-1630. doi: 10.21037/tlcr-23-215. Epub 2023 Jun 5. [Article]
- FDA Approved Drug Products: Imdelltra (tarlatamab-dlle) for intravenous injection [Link]
- BioSpace: FDA APPROVES IMDELLTRA™ (TARLATAMAB-DLLE), THE FIRST AND ONLY T-CELL ENGAGER THERAPY FOR THE TREATMENT OF EXTENSIVE-STAGE SMALL CELL LUNG CANCER [Link]
- External Links
- 2682955
- Wikipedia
- Tarlatamab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Available Not Available Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide 3 Recruiting Treatment Extensive-stage Small Cell Lung Cancer (SCLC) / Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide 3 Recruiting Treatment Small Cell Lung Cancer (SCLC) / Small Cell Lung Cancer, Limited Stage 1 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Relapsed/Refractory Small Cell Lung Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution; kit Intravenous 0.9 mg/1mg Injection, powder, lyophilized, for solution; kit Intravenous 2.4 mg/1mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderAntibody
- General Function
- Inhibits primary neurogenesis. May be required to divert neurons along a specific differentiation pathway. Plays a role in the formation of somite boundaries during segmentation of the paraxial mesoderm (By similarity)
- Specific Function
- Calcium ion binding
- Gene Name
- DLL3
- Uniprot ID
- Q9NYJ7
- Uniprot Name
- Delta-like protein 3
- Molecular Weight
- 64616.855 Da
References
- FDA Approved Drug Products: Imdelltra (tarlatamab-dlle) for intravenous injection [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderAntibody
- General Function
- Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells (PubMed:12215456)
- Specific Function
- Identical protein binding
Components:
References
- FDA Approved Drug Products: Imdelltra (tarlatamab-dlle) for intravenous injection [Link]
Drug created at November 30, 2022 18:23 / Updated at August 23, 2024 02:37