LAG-3
LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma.
Relatlimab plus nivolumab (Opdualag) improved PFS over nivolumab alone in melanoma (RELATIVITY-047). Fianlimab and favezelimab are in phase 3 across tumours.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma.
- 1 · What it is
LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma.
- 2 · What goes wrong in cancer
Binds MHC class II and FGL1; co-expressed with PD-1 on exhausted T cells.
- 3 · How drugs use it
2 products aim at LAG-3: antibodies and bispecific antibodies. Checkpoint drugs are antibodies that cover one side of an immune ‘stand down’ handshake so T cells stay active.
Biology
Binds MHC class II and FGL1; co-expressed with PD-1 on exhausted T cells.
- Exhausted T cells
How common it is, by cancer
Fianlimab is Regeneron's LAG-3 blocker. Promising early data with cemiplimab did not hold up against pembrolizumab in a first-line phase 3 in 2026.
Opdualag combines relatlimab, the first drug targeting the LAG-3 immune brake, with nivolumab for melanoma.
Before 2011 median survival in metastatic melanoma was under a year; this trial shows that roughly half of patients treated with combination checkpoint blockade are now long-term survivors, effectively cured. It anchors first-line treatment of advanced melanoma and sets the benchmark for every new regimen, including nivolumab-relatlimab. The combination's toxicity means nivolumab alone or newer doublets remain reasonable for some patients.
Patients with newly diagnosed advanced melanoma have a dual-checkpoint option that improves on nivolumab alone with only a modest increase in serious side effects, making it attractive for those unable to tolerate or unwilling to risk the toxicity of ipilimumab. It did not prove superior survival, and it has not been compared with nivolumab plus ipilimumab, which remains preferred for patients with brain metastases or other high-risk features. LAG-3 is now an established target under study in many other cancers.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetCTLA-4
Shares VISTA, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Hallmark: avoiding immune destruction, Immune checkpoint and the tag checkpoint.
- TargetPD-1
Shares Fianlimab + cemiplimab phase 3 (first-line melanoma), RELATIVITY-047, TIM-3, VISTA and the tag checkpoint.
- TargetTIGIT
Shares TIM-3, Immune checkpoint, T-cell exhaustion, PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag checkpoint.
- TargetPD-L1
Shares Hallmark: avoiding immune destruction, Immune checkpoint, T cell, T-cell exhaustion and the tag checkpoint.
- TargetCD47
Shares Cold tumours and the immunosuppressive microenvironment and the tag checkpoint.
- TrialCheckMate 067
Shares RELATIVITY-047, RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later.
- ProductCemiplimab
Shares Fianlimab, Fianlimab + cemiplimab phase 3 (first-line melanoma), Melanoma, Immune checkpoint inhibitors.
- CompanyRegeneron
Shares Fianlimab, Fianlimab + cemiplimab phase 3 (first-line melanoma), Melanoma.