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

This phase I trial evaluated the IDO1 enzyme inhibitor, BMS-986205, with radiation (RT) and nivolumab treatment in newly diagnosed patients with GBM IDHwt. Cohort A received RT + nivolumab with escalating BMS-986205 doses in MGMT unmethylated GBM patients. Cohort B received the highest dose of BMS-986205 with nivolumab and standard RT/temozolomide (TMZ) TMZ in MGMT methylated GBM patients. The treatments were found to be safe and tolerable. The median overall survival was 11.5 (95% CI: 3.71, 33.8) and 26.9 months (95% CI: 8.94-NR) while the 2-year survival rates were 33% (95% CI: 10.3%, 58.8%) and 60% (95% CI: 12.6%, 88.2%) for MGMT unmethylated and methylated GBM, respectively. Longer 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).