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Identification
- Summary
Tislelizumab is an IgG4 variant monoclonal antibody against PD-1 indicated for the treatment of unresectable, locally advanced or metastatic esophageal squamous cell carcinoma
- Brand Names
- Tevimbra
- Generic Name
- Tislelizumab
- DrugBank Accession Number
- DB14922
- Background
Tislelizumab is a humanized monoclonal IgG4 antibody against programmed death receptor-1 (PD-1). It was engineered to have a nullified Fc portion, thus minimizing binding to FcγR on macrophages and limiting treatment resistance via antibody-dependent phagocytosis.1 By blocking PD-L1/PD-L2–mediated cell signaling, tislelizumab restores T-cell function through cytokine production, resulting in immune-mediated antitumor responses.2 Tislelizumab is generally well tolerated with manageable and mild-to-moderate adverse effects.3
On September 25, 2023, tislelizumab gained EMA approval as a monotherapy for adults with esophageal cancer under the brand name TEVIMBRA. This approval was based on positive results demonstrated in the RATIONALE 302 study, where an 8.6-month median overall survival rate was observed for tislelizumab treatment compared to 6.3-month for chemotherapy.5 Tislelizumab was also approved by the FDA on March 14, 2024.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
>SUBUNIT_1 QVQLQESGPGLVKPSETLSLTCTVSGFSLTSYGVHWIRQPPGKGLEWIGVIYADGSTNYN PSLKSRVTISKDTSKNQVSLKLSSVTAADTAVYYCARAYGNYWYIDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGGPSVFL FPPKPKDTLMISRTPEVTCVVVAVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV VSVLTVVHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_2 QVQLQESGPGLVKPSETLSLTCTVSGFSLTSYGVHWIRQPPGKGLEWIGVIYADGSTNYN PSLKSRVTISKDTSKNQVSLKLSSVTAADTAVYYCARAYGNYWYIDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGGPSVFL FPPKPKDTLMISRTPEVTCVVVAVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV VSVLTVVHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_3 DIVMTQSPDSLAVSLGERATINCKSSESVSNDVAWYQQKPGQPPKLLINYAFHRFTGVPD RFSGSGYGTDFTLTISSLQAEDVAVYYCHQAYSSPYTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4 DIVMTQSPDSLAVSLGERATINCKSSESVSNDVAWYQQKPGQPPKLLINYAFHRFTGVPD RFSGSGYGTDFTLTISSLQAEDVAVYYCHQAYSSPYTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- NIH Inxight: Tislelizumab [Link]
- Synonyms
- Tislelizumab
- External IDs
- BGB-A317
Pharmacology
- Indication
Tislelizumab is indicated as monotherapy for the treatment of unresectable,4,6 locally advanced,4 or metastatic esophageal squamous cell carcinoma 4,6 in adults after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor, such as platinum-based chemotherapy.4,6
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Locally advanced unresectable esophageal squamous cell carcinoma •••••••••••• ••••• •••••••• •••••••••••••• •••••••••••• ••••••••• ••••••••••• Treatment of Metastatic esophageal squamous cell carcinoma •••••••••••• ••••• •••••••• •••••••••••• Treatment of Unresectable esophageal squamous cell carcinoma •••••••••••• ••••• •••••••• •••••••••••• Treatment of Unresectable, metastatic esophageal squamous cell carcinoma (escc) •••••••••••• ••••• •••••••• •••••••••••••• •••••••••••• ••••••••• ••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Tislelizumab decreased tumour growth in xenograft models and a human PD-1 transgenic mouse model.6
- Mechanism of action
Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.6
Tislelizumab is a humanized immunoglobulin G4 (IgG4) variant monoclonal antibody against PD-1, binding to the extracellular domain of human PD-1. It competitively blocks the binding of both PD-L1 and PD-L2, inhibiting PD-1-mediated negative signalling and enhancing the functional activity in T cells in in vitro cell-based assays.4
Target Actions Organism AProgrammed cell death protein 1 inhibitorantibodyHumans - Absorption
The pharmacokinetics (PK) of tislelizumab were characterized using population PK analysis with concentration data from 2 596 patients with advanced malignancies who received tislelizumab doses of 0.5 to 10 mg/kg every 2 weeks, 2.0 and 5.0 mg/kg every 3 weeks, and 200 mg every 3 weeks.4
The time to reach 90% steady-state level is approximately 84 days (12 weeks) after 200 mg doses once every 3 weeks, and the steady-state accumulation ratio of tislelizumab PK exposure is approximately 2-fold.4
Tislelizumab is administered intravenously and therefore is immediately and completely bioavailable.4
- Volume of distribution
A population pharmacokinetic analysis indicates that the steady-state volume of distribution is 6.42 L, which is typical of monoclonal antibodies with limited distribution.4
- Protein binding
Little information is available on the protein binding of tislelizumab.
- Metabolism
Tislelizumab is expected to be degraded into small peptides and amino acids via catabolic pathways.4
- Route of elimination
Not Available
- Half-life
Based on population PK analysis, the geometrical mean terminal half-life of tislelizumab was approximately 23.8 days with a coefficient variation (CV) of 31%.4
- Clearance
Based on population PK analysis, the clearance of tislelizumab was 0.153 l/day with an interindividual variability of 26.3%.4
- Adverse Effects
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There are no available data on the use of tislelizumab in pregnant women. Based on its mechanism of action, tislelizumab can cause fetal harm when administered to a pregnant woman.4
Animal reproduction studies have not been conducted with tislelizumab. However, in murine models of pregnancy, blockade of PD-1/PD-L1 signaling has been shown to disrupt tolerance to the fetus and result in increased fetal loss.4
Human IgG4 (immunoglobulins) are known to cross the placental barrier. Therefore, tislelizumab, being an IgG4 variant, has the potential to be transmitted from the mother to the developing fetus.4
Women should be advised of the potential risk to a fetus. Tislelizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with tislelizumab.4
No clinical data are available on the possible effects of tislelizumab on fertility. No reproductive and development toxicity studies have been conducted with tislelizumab. Based on a 3-month repeat-dose toxicity study, there were no notable effects in the male and female reproductive organs in cynomolgus monkeys when tislelizumab was given at doses of 3, 10, or 30 mg/kg every 2 weeks for 13 weeks (7 dose administrations).4
There is no information on overdose with tislelizumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse drug 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Tislelizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Tislelizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Tislelizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tislelizumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Tislelizumab. - 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 Tevimbra Injection, solution, concentrate 10 mg/1mL Intravenous Beigene Usa, Inc. 2024-03-14 Not applicable US 
Tevimbra Injection, solution, concentrate 10 mg/ml Intravenous Bei Gene Ireland Limited 2024-07-17 Not applicable EU 
Tevimbra Injection, solution, concentrate 10 mg/ml Intravenous Bei Gene Ireland Limited 2024-07-17 Not applicable EU Tizveni Injection, solution, concentrate 100 mg Intravenous Bei Gene Ireland Limited 2024-07-10 2024-02-22 EU Tizveni Injection, solution, concentrate 100 mg Intravenous Bei Gene Ireland Limited 2024-07-10 2024-02-22 EU
Categories
- ATC Codes
- L01FF09 — Tislelizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immune Checkpoint Inhibitors
- Immunoglobulins
- Immunoproteins
- Monoclonal antibodies and antibody drug conjugates
- PD-1/PD-L1 (Programmed cell death protein 1/death ligand 1) inhibitors
- PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors
- Proteins
- Serum Globulins
- 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
- 0KVO411B3N
- CAS number
- 1858168-59-8
References
- General References
- Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E: Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. J Clin Oncol. 2022 Sep 10;40(26):3065-3076. doi: 10.1200/JCO.21.01926. Epub 2022 Apr 20. [Article]
- Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, Zhang Y, Zhou X, Wang Z, Wang Y, Shi Y, Bai H, Liu N, Yang X, Cui X, Cao Y, Liu Q, Song J, Li Y, Tang Z, Guo M, Wang L, Li K: The binding of an anti-PD-1 antibody to FcgammaRIota has a profound impact on its biological functions. Cancer Immunol Immunother. 2018 Jul;67(7):1079-1090. doi: 10.1007/s00262-018-2160-x. Epub 2018 Apr 23. [Article]
- Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M: Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020 Jun;8(1):e000453. doi: 10.1136/jitc-2019-000453. [Article]
- EMA Approved Drug Products: Tevimbra (tislelizumab) concentrate for solution for intravenous infusion [Link]
- Anti-PD-1 antibody gains EU approval for oesophageal cancer [Link]
- FDA Approved Drug Products: TEVIMBRA (tislelizumab-jsgr) injection, for intravenous use [Link]
- OncLive: FDA Approves Tislelizumab for Advanced or Metastatic ESCC After Chemotherapy [Link]
- External Links
- 2677426
- Wikipedia
- Tislelizumab
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 Active Not Recruiting Not Available Chemotherapy / First-Line / Stage IV Gastric Cancer / Tislelizumab 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Hepatocellular Carcinoma 1 somestatus stop reason just information to hide Not Available Completed Not Available Anti-PD-1 Antibody / Hepatocellular Carcinoma / Liver Disease 1 somestatus stop reason just information to hide Not Available Completed Treatment Extranodal NK/T-cell Lymphoma, Nasal Type 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Not Available Colorectal Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 10 mg/ml Injection, solution, concentrate Intravenous 10 mg/1mL Injection, solution, concentrate Intravenous 100 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorAntibody
- General Function
- Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (By similarity)
- Specific Function
- signaling receptor activity
- Gene Name
- PDCD1
- Uniprot ID
- Q15116
- Uniprot Name
- Programmed cell death protein 1
- Molecular Weight
- 31646.635 Da
References
- EMA Approved Drug Products: Tevimbra (tislelizumab) concentrate for solution for intravenous infusion [Link]
Drug created at May 20, 2019 14:35 / Updated at July 18, 2024 12:20