Abstract Background. We conducted a phase 1 trial to evaluate radiotherapy (RT) and nivolumab with the further addition of an IDO1 enzyme inhibitor (BMS-986205) in newly diagnosed patients with GBM IDHwt. Methods. In the current study, there were two primary cohorts of individuals. Cohort A included MGMT unmethylated GBM patients who received RT with concurrent and adjuvant nivolumab with escalating BMS-986205 doses. Cohort B included MGMT methylated GBM patients who received BMS-986205 at 25mg daily with RT, nivolumab, and temozolomide (TMZ) followed by adjuvant TMZ. Patient outcomes were correlated with flow cytometric, transcriptome, general metabolite, and microbial metabolite analyses. Results. The treatments for both cohorts were moderately safe and tolerable. The treatment emergent adverse events (TEAE) mostly related to RT, TMZ, or the underlying disease and tumor progression. In cohort A, serious AEs and TEAEs were predominantly lower grade with no differences between the IDO1 enzyme inhibitor dosing cohorts. Dose-limiting toxicities (DLTs) reflected by increased transaminases (grade 3) were observed in 2 and 3 patients at 50mg and 100mg levels of BMS-986205, respectively, with malaise observed in the 50mg arm only. The 50mg daily schedule was established as the recommended phase 2 dose (RP2D) in combination with RT and nivolumab. A number of exploratory correlative studies were also conducted. Conclusions. This single arm small phase 1 trial establishes a safety profile and RP2D for RT in combination with nivolumab and BMS-986205 for newly diagnosed MGMT-unmethylated GBM patients. (ClinicalTrials.gov: NCT04047706).
Lukas et al. (Tue,) studied this question.