# Caution: LAG-3 blockade outside active disease

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

## TL;DR

LAG-3 blockers helped in measurable melanoma with one drug pairing, but failed as adjuvant therapy and with a different PD-1 partner.

## Summary

This caution notes that LAG-3 blockade in melanoma has succeeded in only one setting: relatlimab with nivolumab in unresectable, measurable disease, as shown in RELATIVITY-047. The same pairing failed as adjuvant therapy in RELATIVITY-098, and the alternative LAG-3 antibody fianlimab with cemiplimab failed in a first-line phase 3 reported in 2026. LAG-3 is expressed on exhausted T cells inside tumours, so without tumour present, or with different antibody properties and comparators, the effect may vanish. Two negative phase 3 trials against one positive one mean the benefit cannot be assumed to transfer to the adjuvant setting or to a different PD-1 partner.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Relatlimab + nivolumab + Fianlimab
- Type: caution
- Rationale: LAG-3 is expressed on exhausted T cells inside tumours; without tumour, or with different antibody properties and comparators, the effect may vanish.
- Evidence: Two negative phase 3 trials versus one positive.

## Sources

- ClinicalTrials.gov NCT03470922: RELATIVITY-047: https://clinicaltrials.gov/study/NCT03470922
- ClinicalTrials.gov NCT05002569: RELATIVITY-098: https://clinicaltrials.gov/study/NCT05002569

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- targets: [LAG-3](https://onco.cc/targets/lag3/)
- drugs: [Fianlimab](https://onco.cc/drugs/fianlimab/), [Relatlimab + nivolumab](https://onco.cc/drugs/relatlimab-nivolumab/)
- 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/)

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