LAG-3
LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma. This dossier gathers the 2 products (1 approved), 3 trials, 2 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Binds MHC class II and FGL1; co-expressed with PD-1 on exhausted T cells.
- Exhausted T cells
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →Products by modality and phase
Browse products →| Modality | Approved | Phase 3 |
|---|---|---|
| Antibody 1 | — | |
| Bispecific antibody 1 | — |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| Fianlimab + cemiplimab phase 3 (first-line melanoma) NCT05352672 | 3 | Negative | Untreated unresectable or metastatic melanoma: fianlimab + cemiplimab (two dose levels) vs pembrolizumab | Primary PFS endpoint not met; numerical +5.1 months median PFS at the high dose. | |
| RELATIVITY-098 NCT05002569 | 3 | Negative | Resected stage III/IV melanoma: adjuvant nivolumab + relatlimab vs nivolumab | RFS not improved. | |
| RELATIVITY-047 NCT03470922 | 2/3 | Positive | Untreated unresectable or metastatic melanoma: nivolumab + relatlimab (fixed dose) vs nivolumab | PFS HR 0.75; median OS 51.0 vs 34.1 months. |
Resistance routes that involve this target
Unaddressed routes →Exhausted T cells co-express other inhibitory receptors.
- Relatlimab + nivolumab (LAG-3) works; TIGIT combinations failed
Pathways where it is a node
Pathway-to-drug matrix →- PD-1 / PD-L1 immune checkpoint & T-cell activationNode: LAG-3 / TIGIT · 4 druggable nodes
How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.
Which nodes have drugs → - T-cell exhaustionNode: Checkpoint blockade · 3 druggable nodes
T cells that see their target for weeks on end without winning gradually shut down: they raise a set of brakes (PD-1, LAG-3, TIM-3, TIGIT), lose their ability to kill, and eventually lock this state into their DNA. Checkpoint drugs rescue the ones that are only partly exhausted; the terminally exhausted are beyond reach.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later · New England Journal of Medicine 2025
- RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma · New England Journal of Medicine 2022
Query for this target: (TITLE:"LAG-3" OR ABSTRACT:"LAG-3" OR TITLE:"LAG3" OR ABSTRACT:"LAG3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about LAG-3, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/lag3.json. Licence CC BY 4.0.