Newly diagnosed glioblastoma IDHwt patients treated with radiation, nivolumab, and BMS-986205

This phase I trial evaluated IDO1 enzyme inhibitor BMS-986205 combined with radiation (RT) and nivolumab treatment in newly diagnosed patients with GBM IDHwt. Cohort A received RT + nivolumab with escalating doses of BMS-986205 in patients with MGMT unmethylated GBM (n=12). Cohort B received the highest dose of BMS-986205 combined with standard RT/temozolomide (TMZ)->TMZ in patients with MGMT methylated GBM (n=6). The treatments were found to be safe and tolerable. The median overall survival (mOS) was 11.5 (95% CI: 3.71, 33.8) and 26.9 months (95% CI: undefined) while the 2-year survival rates were 33% (95% CI: 10.3%, 58.8%) and 60% (95% CI: 12.6%, 88.2%) for unmethylated and methylated tumors, respectively. Increased patient survival was associated with higher CD8+ T cell levels, higher microbial aryl-lactate levels, higher abundance of Massilioclostridium coli, Dysosmobacter welbionis, and Phocaeicola plebeius in the stool, a younger age, and a lack of gross total resection . (ClinicalTrials.gov: NCT04047706).