# LAG-3

Source: https://onco.cc/targets/lag3/  
OnCo record `lag3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma.

## Summary

LAG-3 is an inhibitory receptor that binds MHC class II and FGL1 and is co-expressed with PD-1 on exhausted T cells, so blocking both releases two brakes on the same cell. Relatlimab plus nivolumab (Opdualag) improved progression-free survival over nivolumab alone in untreated advanced melanoma in RELATIVITY-047, with less toxicity than the ipilimumab combination, making LAG-3 the third immune checkpoint to reach approval. LAG-3 expression of at least 1 percent on immune cells was seen in roughly 75 to 80 percent of the RELATIVITY-047 population. Fianlimab and favezelimab are in phase 3 across tumour types, and whether the benefit extends beyond melanoma is the central open question. For a newcomer: LAG-3 is the immune brake that joined PD-1 blockade to make melanoma immunotherapy work better without much extra toxicity.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: checkpoint
- Symbol: LAG3
- Class: checkpoint
- Biology: Binds MHC class II and FGL1; co-expressed with PD-1 on exhausted T cells.
- Where found: Exhausted T cells

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/LAG3
- Wikipedia: https://en.wikipedia.org/wiki/LAG3

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/)
- drugs: [Favezelimab](https://onco.cc/drugs/favezelimab/), [Fianlimab](https://onco.cc/drugs/fianlimab/), [HLX26](https://onco.cc/drugs/hlx26/), [Relatlimab + nivolumab](https://onco.cc/drugs/relatlimab-nivolumab/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [T-cell exhaustion](https://onco.cc/pathways/t-cell-exhaustion/)
- trials: [Fianlimab + cemiplimab phase 3 (first-line melanoma)](https://onco.cc/trials/fianlimab-phase3-melanoma/), [RELATIVITY-047](https://onco.cc/trials/relativity-047/), [RELATIVITY-098](https://onco.cc/trials/relativity-098/)
- pairings: [Caution: LAG-3 blockade outside active disease](https://onco.cc/pairings/lag3-adjuvant-caution/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [LAG-3 blockade](https://onco.cc/technologies/lag3-blockade/)
- people: [Hussein A. Tawbi](https://onco.cc/people/hussein-tawbi/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Hallmark: avoiding immune destruction](https://onco.cc/terms/avoiding-immune-destruction/), [Immune checkpoint](https://onco.cc/terms/immune-checkpoint/), [T cell](https://onco.cc/terms/t-cell/)
- targets: [FGL1](https://onco.cc/targets/fgl1/), [TIM-3](https://onco.cc/targets/tim3/), [VISTA](https://onco.cc/targets/vista/)
- key papers: [CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma](https://onco.cc/key-papers/paper-checkmate-067-10-year-nejm-2025/), [Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy](https://onco.cc/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/), [RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma](https://onco.cc/key-papers/paper-relativity-047-nejm-2022/)
- institutions: [Istituto Nazionale Tumori IRCCS Fondazione G. Pascale](https://onco.cc/institutions/pascale-naples/), [UPMC Hillman Cancer Center](https://onco.cc/institutions/upmc-hillman/)
- companies: [Immutep](https://onco.cc/companies/immutep/)

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