Dose-Escalation Study Supports Phase 2 Development of BMS-986205 Plus Radiotherapy and Nivolumab in Glioblastoma
Clinical Summary:
- Design/Population: This phase 1 study evaluated radiotherapy plus nivolumab with escalating doses of the IDO1 inhibitor BMS-986205 in patients with newly diagnosed IDH-wild-type glioblastoma.
- Key Outcomes: The combination demonstrated a manageable safety profile across treatment cohorts. Dose-limiting toxicities occurred at higher dose levels, and 50 mg once daily of BMS-986205 was established as the recommended phase 2 dose for patients with MGMT-unmethylated glioblastoma.
- Clinical Relevance: These findings support further evaluation of radiootherapy, nivolumab, and BMS-986205 in newly diagnosed glioblastoma and establish a recommended phase 2 dose for future clinical development.
Results from a phase 1 trial demonstrated that radiotherapy plus nivolumab and the IDO1 inhibitor BMS-986205 was generally well tolerated in patients with newly diagnosed IDH-wild-type glioblastoma, establishing a recommended phase 2 dose for further clinical evaluation.
In this single-arm trial, patients were assigned to cohorts according to MGMT methylation status. Patients with MGMT-unmethylated glioblastoma received escalating doses of BMS-986205 plus radiotherapy with concurrent and adjuvant nivolumab, whereas patients with MGMT-methylated disease received 25 mg of once daily BMS-986205 plus radiotherapy, nivolumab, and temozolomide followed by adjuvant temozolomide. Primary end points included safety and recommended phase 2 dose.
The combination was generally well tolerated across both treatment cohorts. Most treatment-emergent adverse events were attributed to radiotherapy, temozolomide, the underlying disease, or tumor progression. Among patients with MGMT-unmethylated disease, serious adverse events and treatment-emergent adverse events were predominantly low grade, with similar safety findings across the BMS-986205 dose-escalation cohorts. Dose-limiting toxicities consisted primarily of grade 3 transaminase elevations, which occurred in 2 patients treated with 50 mg of BMS-986205 and 3 patients treated with 100 mg. Malaise was observed only in the 50-mg cohort.
Based on the overall safety findings, investigators established 50 mg once daily as the recommended phase 2 dose of BMS-986205 in combination with radiotherapy and nivolumab for patients with MGMT-unmethylated glioblastoma.
“This single-arm, small phase 1 trial establishes a safety profile and [recommended phase 2 dose for radiotherapy] in combination with nivolumab and BMS-986205 for newly diagnosed patients with MGMT-unmethylated [glioblastoma],” concluded study authors.
Source:
Lukas RV, Zhai L, Lauing KL, et al. Phase I evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205. Clin Cancer Res. Published online: June 12, 2026. doi: 10.1158/1078-0432.CCR-26-1124
