Trial results for nivolumab in patients with IDH-mutant gliomas were posted on ClinicalTrials.gov on 2025-11-24. The study investigated outcomes in cohorts with and without hypermutator phenotype. The 6-month progression-free survival rate was 25.0% for the hypermutated phenotype cohort and 40.0% for the non-hypermutated phenotype cohort.
Background
Gliomas are a common type of malignant brain tumor. A subset of these tumors carries mutations in the isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) genes. A high number of mutations within a tumor defines a hypermutator phenotype (HMP). Nivolumab is an immunotherapy designed to help the immune system combat cancer.
Trial design
The Phase 2 study (NCT03718767) investigated nivolumab in patients with IDH-mutant gliomas. The trial enrolled 62 participants with conditions including Glioma, Glioblastoma, High Grade Glioma, Low Grade Glioma, and Malignant Glioma. Participants were divided into two cohorts: those with a hypermutator phenotype (HMP) and those with a non-hypermutated phenotype (NHMP). The study aimed to assess tumor growth control and progression-free survival.
Key results
The trial reported median progression-free survival (PFS) rates at 6 months for both cohorts:
- For the Cohort 1/Hypermutated Phenotype (HMP), the median PFS rate at 6 months was 25.0%.
- For the Cohort 2/Non-hypermutated Phenotype (NHMP), the median PFS rate at 6 months was 40.0%.
Mean symptom interference scores, measured by the MD Anderson Symptom Inventory-Brain Tumor Module (MDSAI-BT) per treatment cycle, were also reported. For Cohort 1/HMP, mean scores ranged from 2.33 (Standard Deviation: 1.99) to 3.96 (Standard Deviation: 2.96). For Cohort 2/NHMP, mean scores ranged from 2.06 (Standard Deviation: 2.80) to 2.46 (Standard Deviation: 2.03).
Key analyses included Cox regression, which reported a Hazard Ratio (HR) of 1.0 (p-value: 0.623) and another HR of 1.73 (p-value: 0.073).
What this means
The results from this Phase 2 study indicate differences in 6-month progression-free survival rates between IDH-mutant glioma patients with and without a hypermutator phenotype when treated with nivolumab. The non-hypermutated phenotype cohort showed a higher 6-month PFS rate compared to the hypermutated phenotype cohort. Symptom interference scores also varied between the groups. These findings provide initial insights into the potential differential effects of nivolumab based on the hypermutator status in IDH-mutant gliomas, warranting further investigation.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03718767, titled "Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype," were posted on 2025-11-24 on clinicaltrials.gov.