Lead-in therapy targeting PD1 and/or LAG3 imposes distinct immune phenotypes in first-line treatment of metastatic melanoma.

ABSTRACT: Simultaneous blockade of lymphocyte activation gene-3 (LAG-3) and programmed-death-1 (PD-1) pathways enhance anti-tumor activity in patients with melanoma. It is not known if this immunotherapy induces unique immune modulation or how this may relate to clinical outcomes, compared to the single modalities. We conducted a randomized three-arm phase 2 trial (NCT03743766) in advanced melanoma comparing lead-in treatment with one cycle of relatlimab- (n=14), nivolumab-(n=15), and nivolumab-relatlimab (n=14) as first-line therapy, followed by combination nivolumab-relatlimab, to assess the impact of the lead-in therapy on immune populations, related to objective response rate, progression-free survival (PFS) and major pathologic response on biopsy (MPRbx). Unexpectedly, diminished efficacy was o

SUBMITTER: Karapetyan L 

PROVIDER: S-EPMC12637783 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature