IO102-IO103 (PD-L1/IDO peptide vaccine) + nivolumab–relatlimab (PD-1/LAG-3) posts 60% ORR in 1L unresectable melanoma

IO102-IO103 is a subcutaneous peptide vaccine targeting PD-L1 and IDO-expressing tumor and immunosuppressive cells, combined here with nivolumab–relatlimab (dual PD-1/LAG-3 checkpoint blockade) in a multicenter Phase 2 trial in previously untreated, unresectable non-uveal melanoma (NCT05912244). In 43 evaluable patients, best overall response rate (RECIST v1.1) was 60% (95% CI 44-75%; 16% CR, 44% PR); at Dec 1, 2025 data lock with 10.1 months median follow-up, median PFS was 8.2 months (95% CI 6.8-NR) and median DOR was NR (95% CI 14-NR). Grade 3-4 TRAEs occurred in 21% (no treatment-related deaths); for context, nivo–rela alone in RELATIVITY-047 reported ORR ~43% and median PFS ~10.1-10.2 months with grade 3-4 TRAEs in the high-teens range—so the response rate looks higher here, but the PFS signal is not clearly better (and follow-up/sample size are limited), including in PD-L1–negative tumors where ORR was 52% (n=25) and median PFS remained 8.2 months.