Анти-LAG-3 терапия показала приемлемую безопасность и признаки эффективности при рецидивирующем глиобластоме

The anti–lymphocyte activation gene 3 (LAG-3) antibody relatlimab demonstrated acceptable safety with or without nivolumab, and also provided preliminary immunologic and clinical findings for patients with recurrent glioblastoma (GBM), according to results reported in the journal Nature Medicine. “In the present study, the primary endpoint of safety was met; relatlimab monotherapy and combination relatlimab with nivolumab were well tolerated with the dosages described,” the study investigators wrote. The multicenter, open-label, phase 1 ABTC 1501 study (NCT02658981) assessed the safety and preliminary activity of relatlimab, with or without nivolumab, in adjuvant therapy for patients with recurrent GBM. The primary endpoint was safety, based on determination of the maximum tolerated dose (MTD) across dose ranges for relatlimab and the relatlimab/nivolumab combination in this population. Additionally, some patients also received neoadjuvant relatlimab as monotherapy or with nivolumab. Neoadjuvant therapy was administered 10 + 3 days before surgery. The study included 46 patients who received treatment and were included in per-protocol, safety, and efficacy analyses. Patients were divided equally into the relatlimab and relatlimab-nivolumab cohorts. The median age was 55 years (range, 21.9-76.8 years). Prior surgery included gross total resection in 37 patients (80.4%) and subtotal resection in 9 patients (19.6%). Six patients also received neoadjuvant relatlimab, and 7 also received neoadjuvant relatlimab-nivolumab. The study’s primary endpoint was met. The MTD for relatlimab was identified to be 800 mg monotherapy, and 160 mg of relatlimab with 240 mg of nivolumab for the combination. No patients experienced dose-limiting toxicities (DLTs) in the monotherapy arm receiving compared with 6 (26%) who were treated with the combination therapy in various dosing regimens. These DLTs included worsened cerebral edema (n=2), grade 3 muscle weakness, grade 3 hypertension, grade 3 syncope, and grade 3 thyroiditis (n=1 patient each) Twelve-month overall survival (OS) rates were 34.8% among patients who received relatlimab monotherapy and 52.2% among patients who received relatlimab-nivolumab combination therapy. “Although the study was not designed or powered to formally assess survival, the combination relatlimab and nivolumab arm demonstrated a 12-month OS of 52% (95% confidence interval: 31-73), with 5 of 46 patients (11%) exhibiting extended survival beyond 24 months,” the researchers wrote. Investigators observed increased intratumoral CD8+ T-cell infiltration for patients of both the monotherapy and combination therapy groups who received neoadjuvant administration. Additional exploratory analyses suggested that, among patients who received adjuvant relatlimab-nivolumab combination therapy, there was evidence of elevated baseline interferon signaling in biopsy specimens from long-term survivors (OS longer than 24 months) compared with biopsies of patients with OS under 9 months. There was also evidence of increased T-cell clonality in specimens from patients considered long-term responders (surviving more than 24 months) compared with specimens from nonresponding patients with survival under 9 months. Disclosures: This research was supported by the Adult Brain Tumor Consortium, Bristol Myers Squibb, the National Cancer Institute, the National Institutes of Health, and the Kelvin Foundation. Some study authors disclosed conflicts of interest. Please see the original reference for complete disclosures. References: Lim M, Ye X, Piotrowski AF, et al. Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial. Nat Med. Published online July 10, 2026. doi:10.1038/s41591-026-04475-7