Dose-Escalation Study Supports Phase 2 Development of BMS-986205 Plus Radiotherapy and Nivolumab in Glioblastoma
Clinical Summary:
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Design/Population: This phase 1 trial evaluated radiotherapy plus nivolumab with escalating doses of the IDO1 inhibitor BMS-986205 in patients with newly diagnosed IDH-wild-type glioblastoma, stratified by MGMT methylation status.
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Key Outcomes: The combination demonstrated a manageable safety profile across treatment cohorts. Dose-limiting toxicities occurred at higher BMS-986205 dose levels, and 50 mg once daily was established as the recommended phase 2 dose for patients with MGMT-unmethylated glioblastoma.
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Clinical Relevance: These findings support further evaluation of radiotherapy, 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 phase 1 trial, patients were assigned to treatment cohorts according to MGMT methylation status. Patients with MGMT-unmethylated glioblastoma received escalating doses of BMS-986205 in combination with radiotherapy and concurrent followed by adjuvant nivolumab. Patients with MGMT-methylated disease received 25 mg of BMS-986205 once daily with radiotherapy, nivolumab, and temozolomide followed by adjuvant temozolomide. The primary end points were safety and determination of the recommended phase 2 dose.
The combination demonstrated a manageable safety profile 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, treatment-emergent and serious adverse events were predominantly low grade and were generally consistent across the BMS-986205 dose-escalation cohorts.
Dose-limiting toxicities primarily consisted of grade 3 transaminase elevations, which occurred in 2 patients receiving 50 mg of BMS-986205 and 3 patients receiving 100 mg. Malaise was reported only in the 50-mg cohort.
Based on the overall safety findings, investigators established 50 mg of once daily BMS-986205 as the recommended phase 2 dose in combination with radiotherapy and nivolumab for patients with MGMT-unmethylated glioblastoma.
As study authors concluded, “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]."
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
