Identification
- Summary
Relatlimab is a monoclonal antibody targeted against LAG-3 which is used in combination with nivolumab for the treatment of unresectable or metastatic melanoma.
- Brand Names
- Opdualag
- Generic Name
- Relatlimab
- DrugBank Accession Number
- DB14851
- Background
Relatlimab is a human IgG4 monoclonal antibody and novel immune checkpoint inhibitor that targets lymphocyte activation gene-3 (LAG-3).3,4 It was the first commercially developed anti-LAG-3 antibody, entering clinical trials in 2013,1 and has garnered interest in the treatment of a variety of cancers, including leukemia2 and melanoma.6 As immune checkpoint inhibitors have limited efficacy when used alone, drugs like relatlimab have been trialed in combination with other checkpoint inhibitors - for example, PD-1 inhibitors like nivolumab or CTLA-4 inhibitors like ipilimumab - to enhance their efficacy.1
Relatlimab received FDA approval in March 2022, alongside the PD-1 inhibitor nivolumab in the combination product Opdualag (Bristol-Myers Squibb), for the treatment of unresectable or metastatic melanoma.4,5 It was the first anti-LAG-3 antibody to demonstrate benefit in a Phase 3 study, as well as the first to receive FDA approval.5 Opdualag was subsequently approved in the European Union in July 20227 and in Canada in September 2023.8
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6472H9940O2026N1704S38
- Protein Average Weight
- 148000.0 Da
- Sequences
>SUBUNIT_1 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWNWIRQPPGKGLEWIGEINHRGSTNSN PSLKSRVTLSLDTSKNQFSLKLRSVTAADTAVYYCAFGYSDYEYNWFDPWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG
>SUBUNIT_2 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWNWIRQPPGKGLEWIGEINHRGSTNSN PSLKSRVTLSLDTSKNQFSLKLRSVTAADTAVYYCAFGYSDYEYNWFDPWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG
>SUBUNIT_3 EIVLTQSPATLSLSPGERATLSCRASQSISSYLAWYQQKPGQAPRLLIYDASNRATGIPA RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGQGTNLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4 EIVLTQSPATLSLSPGERATLSCRASQSISSYLAWYQQKPGQAPRLLIYDASNRATGIPA RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGQGTNLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- NIH Inxight: Relatlimab [Link]
- Synonyms
- Relatlimab
- External IDs
- BMS-986016
Pharmacology
- Indication
Relatlimab is indicated in combination with nivolumab, in the combination product Opdualag, for the treatment of adult and pediatric patients ≥12 years old with unresectable or metastatic melanoma.4 In Canada and the EU, it is specifically indicated as a first-line treatment,8,9 and the EU adds an additional requirement that tumor cell PD-L1 expression be < 1%.9
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 Used in combination to treat Metastatic melanoma Combination Product in combination with: Nivolumab (DB09035) •••••••••••• •••••• ••••••••• ••••• •••••••••• • •• ••••••••• Used in combination to treat Metastatic melanoma Combination Product in combination with: Nivolumab (DB09035) •••••••••••• •••••• ••••••••• ••••••••• Used in combination to treat Metastatic melanoma Combination Product in combination with: Nivolumab (DB09035) •••••••••••• •••••• ••••••••• ••••••••• Used in combination to treat Unresectable melanoma Combination Product in combination with: Nivolumab (DB09035) •••••••••••• •••••• ••••••••• ••••• •••••••••• • •• ••••••••• Used in combination to treat Unresectable melanoma Combination Product in combination with: Nivolumab (DB09035) •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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Relatlimab is administered with nivolumab at 4-week intervals via a 30-minute infusion.4 Infusion-related reactions are uncommon but can be severe - infusion may be interrupted or slowed in patients with mild-to-moderate reactions, but should be discontinued in patients experiencing severe reactions.4 The combination of relatlimab and nivolumab can cause severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, myocarditis, and hypophysitis.4 The early identification and management of immune-mediated adverse reactions is essential for the safe use of this therapy. Additionally, the combination of relatlimab and nivolumab is likely to cause fetal harm when administered to pregnant patients.4 Females of reproductive potential should be advised to use effective contraception throughout treatment and for at least 5 months following the last dose.4
- Mechanism of action
Lymphocyte-activation gene 3 (LAG-3) - also known as CD223 - is a type I transmembrane protein belonging to the immunoglobulin superfamily.1 Its expression on activated T-cells is induced following antigen stimulation,3 and they serve a number of functions including the inhibition of Th1 cell proliferation and the reduction of cytokine production - such as IL-2, IFNγ, and TNF - in these activated T-cells.1 Ligands of LAG-3 include antigen-presenting cells such as MHC class II molecules and liver sinusoidal endothelial cell lectin (LSECtin), the latter of which has been shown to promote tumor progression when expressed on melanoma cells by inhibiting anti-tumor T-cell responses.1
As LAG-3 expression is tied to antigen presentation, continuous antigen exposure owing to chronic infection or tumor-associated antigens can lead to high and sustained expression of LAG-3 on T-cells, which eventually lose their effector functions by becoming functionally "exhausted".3 This loss of T-cell function leads to lessened immunosurveillance and promotes tumor escape.2
Relatlimab is a human IgG4 monoclonal antibody that binds LAG-3 and inhibits its signaling pathway, the antagonism of which promotes T-cell proliferation, cytokine secretion, and, subsequently, restored tumor immunosurveillance.4 Used in combination with nivolumab, a PD-1 receptor blocker, relatlimab has been shown to potentiate the anti-tumor effects of PD-1 blockade.4
Target Actions Organism ALymphocyte activation gene 3 protein antibodyHumans - Absorption
Following once-monthly administration alongside nivolumab, steady-state concentrations of relatlimab were reached after 16 weeks.4 At the recommended dosage, the Cmax and Cavg of relatlimab at steady-state were 62.2 µg/mL and 28.8 µg/mL, respectively.4
- Volume of distribution
The geometric mean volume of distribution of relatlimab at steady-state is 6.6 liters.4
- Protein binding
Not Available
- Metabolism
As with other therapeutic proteins, the metabolism of relatlimab likely occurs via non-specific catabolism to smaller peptides and amino acids.
- Route of elimination
Not Available
- Half-life
The geometric mean effective half-life of relatlimab, when administered alongside nivolumab, is 26.2 days.4
- Clearance
At steady-state, the geometric mean clearance of relatlimab is 5.5 mL/h.4 Clearance at steady-state appears to be approximately 10% lower than after the first dose.4
- Adverse Effects
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No data is available regarding overdosage with relatlimab.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Relatlimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Relatlimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Relatlimab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Relatlimab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Relatlimab. - 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.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Opdualag Relatlimab (80 mg / 20 mL) + Nivolumab (240 mg / 20 mL) Solution Intravenous Bristol Myers Squibb Not applicable Not applicable Canada 
Opdualag Relatlimab (4 mg/1mL) + Nivolumab (12 mg/1mL) Injection Intravenous E.R. Squibb & Sons, L.L.C. 2022-03-18 Not applicable US 
Opdualag Relatlimab (4 mg/ml) + Nivolumab (12 mg/ml) Injection, solution, concentrate Intravenous Bristol Myers Squibb Pharma Eeig 2022-12-02 Not applicable EU 
Categories
- ATC Codes
- L01XY03 — Nivolumab and relatlimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immune Checkpoint Inhibitors
- Immunoglobulins
- Immunoproteins
- Lymphocyte Activation Gene-3 Blocker
- 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
- Humans and other mammals
Chemical Identifiers
- UNII
- AF75XOF6W3
- CAS number
- 1673516-98-7
References
- General References
- Yu X, Huang X, Chen X, Liu J, Wu C, Pu Q, Wang Y, Kang X, Zhou L: Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy. MAbs. 2019 Aug/Sep;11(6):1139-1148. doi: 10.1080/19420862.2019.1629239. Epub 2019 Jun 26. [Article]
- Sordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez-Rodriguez AP, Payer AR, Gonzalez-Garcia E, Lopez-Soto A, Gonzalez S: LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia. Cancers (Basel). 2021 Apr 27;13(9). pii: cancers13092112. doi: 10.3390/cancers13092112. [Article]
- Maruhashi T, Sugiura D, Okazaki IM, Okazaki T: LAG-3: from molecular functions to clinical applications. J Immunother Cancer. 2020 Sep;8(2). pii: jitc-2020-001014. doi: 10.1136/jitc-2020-001014. [Article]
- FDA Approved Drug Products: Opdualag (nivolumab and relatlimab-rmbw) injection for intravenous use [Link]
- BioSpace: U.S. Food and Drug Administration Approves First LAG-3-Blocking Antibody Combination, Opdualag™ (nivolumab and relatlimab-rmbw), as Treatment for Patients with Unresectable or Metastatic Melanoma [Link]
- NIH National Cancer Institute: Nivolumab and Relatlimab Combination Shows Promise in Advanced Melanoma [Link]
- EMA EPAR: Opdualag (relatlimab/nivolumab) [Link]
- Health Canada Product Monograph: Opdualag (nivolumab and relatlimab) solution for intravenous injection [Link]
- EMA Summary of Product Characteristics: Opdualag (nivolumab/relatlimab) solution for intravenous injection [Link]
- External Links
- 2596773
- Wikipedia
- Relatlimab
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous Injection, solution, concentrate Intravenous Solution Intravenous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (By similarity). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (By similarity). Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:8647185).
- Specific Function
- Antigen binding
- Gene Name
- LAG3
- Uniprot ID
- P18627
- Uniprot Name
- Lymphocyte activation gene 3 protein
- Molecular Weight
- 57448.04 Da
References
- FDA Approved Drug Products: Opdualag (nivolumab and relatlimab-rmbw) injection for intravenous use [Link]
Drug created at May 20, 2019 14:30 / Updated at February 14, 2024 00:55