LAG3 lymphocyte activating 3
ENSG00000089692 · protein coding · Open Targets profile
[Lymphocyte activation gene 3 protein]: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:35761082, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as MHC class II, its main ligand present at the surface of antigen-presenting cells (APCs), and FGL1, which is secreted by hepatocytes and certain types of tumor cells (PubMed:30580966, PubMed:32920841, PubMed:35761082, PubMed:39671469, PubMed:7589152, PubMed:8647185, PubMed:9159144). Ligand-binding initiates a signaling that inhibits the T-cell receptor (TCR) in the immunological synapse, preventing T-cell activation (PubMed:40101708). Mechanistically, ligand-binding promotes (1) ubiquitination of the KIEELE motif, unleashing the RRFSALE motif from the membrane and (2) leading to the formation of condensates with the TCR component CD3E, thereby disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:40101708, PubMed:40592325). May inhibit antigen- specific T-cell activation in synergy with PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). 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). {ECO:0000250|UniProtKB:Q61790, ECO:0000269|PubMed:20421648, ECO:0000269|PubMed:30580966, ECO:0000269|PubMed:32920841, ECO:0000269|PubMed:35761082, ECO:0000269|PubMed:39671469, ECO:0000269|PubMed:40101708, ECO:0000269|PubMed:40592325, ECO:0000269|PubMed:7589152, ECO:0000269|PubMed:7805750, ECO:0000269|PubMed:8647185, ECO:0000269|PubMed:9159144}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Antibody
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.5921499729156494 (upper bound 0.8073800206184387). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 158 registry trials, updated in the last three years, of the most advanced drugs against LAG3 (relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Dung LeJohns Hopkins Medical Institution · 2 of 2 trials Phase 2+
- Eric ChristensonJohns Hopkins Sidney Kimmel Comprehensive Cancer Center · 2 of 2 trials Phase 2+
- Georgina LongMelanoma Institute Australia · 2 of 2 trials Phase 2+
- Hussein TawbiM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- James SmithyMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Rodabe N AmariaUT MD Anderson · 2 of 2 trials Phase 2+
- Vincent LamJohns Hopkins University · 1 of 2 trials Phase 2+
- Adanma AyanambakkamUniversity of Oklahoma · 1 of 1 trials Phase 2+
- Adriana KahnYale University · 1 of 1 trials Phase 2+
- Ahmad TarhiniMoffitt Cancer Center · 1 of 1 trials Phase 2+
- Alexander Z WeiColumbia University · 1 of 1 trials Phase 2+
- Allison BetofStanford University · 1 of 1 trials Phase 2+
- Ari RosenbergUniversity of Chicago · 1 of 1 trials Phase 2+
- Arun SinghUCLA / Jonsson Comprehensive Cancer Center · 1 of 1 trials Phase 2+
- Ashley L. WardMacroGenics · 1 of 1 trials Phase 2+
Registry trials of relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimab updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 84 of 148 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 10 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
26 trials of drugs against LAG3 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimab, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 26.
- suspended · 2026-11-03 · National Cancer Institute (NCI) · Relatlimab“Scheduled Interim Monitoring”
- terminated · 2026-11-03 · Columbia University · Fianlimab“Change in standard of care treatment for muscle-invasive bladder cancer”
- suspended · 2026-10-19 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“On hold pending planned interim analysis.”
- withdrawn · 2026-09-14 · Virginia Commonwealth University · Arm 2 cemiplimab and fianlimab“The study was withdrawn because the pharmaceutical company decided not to pursue this combination of drugs following negative data in another indication.”
- withdrawn · 2026-09-03 · Memorial Sloan Kettering Cancer Center · Cemiplimab and Fianlimab“The sponsor is no longer supporting the trial because they are no longer interested in studying the drug in the target patient population.”
- terminated · 2026-08-31 · Merck Sharp & Dohme LLC · Favezelimab/pembrolizumab coformulation“Business Reasons”
- terminated · 2026-08-26 · Bristol-Myers Squibb · Nivolumab-relatlimab FDCNo reason given
- terminated · 2026-07-30 · Immutep S.A.S. · matched by the registry's drug synonyms“Sponsor Decision”
- terminated · 2026-07-28 · Merck Sharp & Dohme LLC · Favezelimab“Business Reason”
- withdrawn · 2026-07-02 · National Health Research Institutes, Taiwan · Nivolumab/Relatlimab“The study was terminated due to administrative reasons following the cancellation of collaboration between the involved parties.”
- terminated · 2026-06-26 · Bristol-Myers Squibb · RelatlimabNo reason given
- suspended · 2026-06-10 · Thomas Jefferson University · Fianlimab“Investigational product is not currently available to the study site.”
- terminated · 2026-05-15 · Iovance Biotherapeutics, Inc. · Nivolumab-relatlimab“After reviewing the available safety and efficacy data to date, Iovance concluded that the study reached the required number of events for evaluation of study endpoints.”
- terminated · 2026-01-08 · Bristol-Myers Squibb · Nivolumab + Relatlimab Fixed Dose Combination“Inability to meet protocol objectives”
- terminated · 2025-10-22 · TriSalus Life Sciences, Inc. · Nivolumab and Relatlimab“The decision was made to terminate the study after the completion of Phase 1 enrollment and not proceed with Phase 2. Trial termination was not due to patient safety or data concerns.”
- terminated · 2025-08-12 · Inge Marie Svane · Relatlimab“Slow recruitment”
- withdrawn · 2025-04-08 · Merck Sharp & Dohme LLC · Favezelimab, Favezelimab/Pembrolizumab“development program discontinuation”
- terminated · 2025-02-14 · Multiple Myeloma Research Consortium · matched by the registry's drug synonyms“Pharmaceutical support has been discontinued.”
- withdrawn · 2024-07-26 · Regeneron Pharmaceuticals · fianlimab“Business Decision”
- terminated · 2024-07-24 · Bristol-Myers Squibb · Relatlimab“Business objectives have changed.”
- withdrawn · 2024-05-06 · National Cancer Institute (NCI) · Relatlimab“No result will be reported- no patient accrued. Status Withdrawn: Study halted prematurely, prior to enrollment of first participant."”
- terminated · 2023-12-20 · MacroGenics · Tebotelimab“Based on internal review of safety data”
- withdrawn · 2023-03-22 · Immutep S.A.S. · matched by the registry's drug synonyms“Replaced by other study NCT05747794”
- terminated · 2021-04-20 · Elizabeth Davis · Relatlimab“Loss of funding”
- terminated · 2021-03-22 · Bristol-Myers Squibb · Relatlimab“The standard of care for the patient population changed and we were unable to accrue any longer.”
Paediatric incentives and obligations for LAG3's drugs
For relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimab: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · LAG3 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-002727-PIP03-23 (nivolumab;relatlimab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 6 May 2024; EMEA-003104-PIP02-22 (Favezelimab;pembrolizumab, Treatment of Hodgkin lymphoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), date not given; EMEA-002727-PIP02-23 (relatlimab;nivolumab, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, hematopoietic and lymphoid tissue neoplasms and melanoma)): W: decision granting a waiver in all age groups for all conditions or indications, 1 Dec 2023; EMEA-003207-PIP01-22 (Fianlimab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 31 Jan 2023; +2 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimabRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Opdualag: authorised since 15 Sept 2022Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Opdualag, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Nivolumab and Relatlimab-rmbw) [Opdualag], 18 Mar 2022: Treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanomaRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 15 interventional studies of relatlimab, fianlimab, eftilagimod alfa, favezelimab, tebotelimab, ieramilimab include patients under 18; 10 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 6 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.