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 demonstrate benefit in a Phase 3 study, as well as the first to receive FDA approval.5

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
References:
  1. NIH Inxight: Relatlimab [Link]
Download FASTA Format
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

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

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

TargetActionsOrganism
ALymphocyte activation gene 3 protein
antibody
Humans
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
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

No data is available regarding overdosage with relatlimab.

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
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
OpdualagRelatlimab (4 mg/1mL) + Nivolumab (12 mg/1mL)InjectionIntravenousE.R. Squibb & Sons, L.L.C.2022-03-18Not applicableUS flag

Categories

Drug Categories
Not Available
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
  1. 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]
  2. 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]
  3. 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]
  4. FDA Approved Drug Products: Opdualag (nivolumab and relatlimab-rmbw) injection for intravenous use [Link]
  5. 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]
  6. NIH National Cancer Institute: Nivolumab and Relatlimab Combination Shows Promise in Advanced Melanoma [Link]
RxNav
2596773
Wikipedia
Relatlimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentMelanoma1
3RecruitingTreatmentNeoplasms, Colorectal1
2Active Not RecruitingTreatmentAdvanced Gastric Cancer1
2Active Not RecruitingTreatmentCancer, Advanced1
2Active Not RecruitingTreatmentCutaneous Melanoma / Mucosal Melanoma / Ocular Melanoma / Stage III Acral Lentiginous Melanoma AJCC v7 / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIB Uveal Melanoma AJCC v7 / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IIIC Uveal Melanoma AJCC v7 / Stage IV Acral Lentiginous Melanoma AJCC v6 and v7 / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Uveal Melanoma AJCC v71
2Active Not RecruitingTreatmentMetastatic Colorectal Cancer (CRC)1
2Active Not RecruitingTreatmentMicrosatellite Stable (MSS) Colorectal Cancer (CRC) / Microsatellite Unstable Colorectal Cancer / Mismatch Repair Deficient Colorectal Cancer / Mismatch Repair Proficient Colorectal Cancer1
2Not Yet RecruitingTreatmentCarcinoma / Renal Medullary Carcinoma1
2Not Yet RecruitingTreatmentMelanoma, Stage II1
2Not Yet RecruitingTreatmentMelanoma / Unresectable Melanoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
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
  1. FDA Approved Drug Products: Opdualag (nivolumab and relatlimab-rmbw) injection for intravenous use [Link]

Drug created at May 20, 2019 14:30 / Updated at March 26, 2022 13:38