LAG-3 blockade
Antibodies against LAG-3, another brake on tired T cells; relatlimab plus nivolumab became the first approved LAG-3 combination for melanoma in 2022.
Overview
Lymphocyte activation gene 3 (LAG-3) is a checkpoint expressed on exhausted T cells that binds MHC class II and fibrinogen-like protein 1. The fixed-dose combination of relatlimab and nivolumab (Opdualag) roughly doubled progression-free survival compared with nivolumab alone in untreated advanced melanoma in the RELATIVITY-047 trial and was approved by the FDA in 2022, the first new checkpoint class since PD-1. Trials in lung, colorectal and other cancers continue, with mixed results.
How it works
Antibodies block LAG-3 binding to its ligands so exhausted T cells regain function, usually combined with PD-1 blockade because the two pathways co-inhibit.
- First new approved checkpoint class after CTLA-4 and PD-1
- Adds efficacy without the toxicity of CTLA-4 combinations
- Benefit shown mainly in melanoma so far
- No validated predictive biomarker
- Overall survival gain modest
Latest papers
topQuery for this technology: (TITLE:"LAG-3 blockade" OR ABSTRACT:"LAG-3 blockade") 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 blockade, not a curated reading list.