Multicenter phase 1 trial of relatlimab with or without nivolumab for recurrent glioblastoma

Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). The multicenter phase 1 ABTC 1501 trial in the US evaluated safety (primary endpoint) and preliminary activity of the anti-LAG-3 antibody relatlimab with or without the anti-PD-1 antibody nivolumab, in patients with recurrent GBM. Forty-six patients were treated (23 per cohort). The primary endpoint of safety was met, with maximum tolerated doses of 800 mg relatlimab for monotherapy and 160 mg relatlimab with 240 mg nivolumab for combination therapy. Treatment-related grade 3-4 adverse events occurred in 6 of 23 patients receiving combination therapy and were not observed with monotherapy. Neoadjuvant administration was associated with increase intratumoral CD8⁺ T cell infiltration for both monotherapy and combination therapy. Exploratory analyses suggested that tumors with elevated baseline interferon signaling and increased T cell clonality were enriched among patients with durable responses to combination therapy. Twelve-month overall survival rate was 34.8% with relatlimab alone and 52.5% with combination therapy; however, this study was not designed to assesss efficacy. The authors conclude that these findings demonstrate an acceptable safety profile and provide preliminary immunologic and clinical signals supporting further evaluation of LAG-3 blockade in GBM.