According to results from a phase 1b trial, the addition of 40 mg of once daily vorasidenib to standard temozolomide demonstrates acceptable safety among patients with IDH 1/2-mutated gliomas.

These findings were presented by Macarena De La Fuente, MD, University of Miami, Florida, at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting in Honolulu, Hawaii.

In this study, investigators enrolled 7 patients with IDH 1/2-mutated gliomas, including astrocytomas (n = 5) and oligodendrogliomas (n = 2), who were eligible to receive temozolomide following radiotherapy or at first recurrence after prior radiotherapy and/or chemotherapy. Patients received standard temozolomide plus 40 mg of once daily vorasidenib in 28-day cycles. Primary end points included safety and recommended phase 2 dose.

At analysis, all patients experienced at least 1 treatment-emergent adverse event, and grade ≥3 adverse events occurred in 2 patients. Adverse events led to 1 dose reduction of vorasidenib (due to grade 2 alanine aminotransferase elevation) and 2 dose reductions of temozolomide (due to myelosuppression). No dose-limiting toxicities were reported, and all patients remained on study treatment. 

Based on safety review committee evaluation, 40 mg of once daily vorasidenib plus standard temozolomide was confirmed as the recommended phase 2 dose.

“In phase 2, approximately 35 participants with newly diagnosed grade 4 mIDH1/2 astrocytoma who have completed radiotherapy + concurrent [temozolomide] will be enrolled and receive vorasidenib + [temozolomide] as post-radiotherapy adjuvant therapy,” concluded Dr De La Fuente et al. “Phase 2 will evaluate the safety and preliminary efficacy of the combination therapy.” 

Source: 

De La Fuente MI, Cloughesy TF, Touat M, et al. Phase 1B study of vorasidenib in combination with temozolomide in participants with IDH1- or IDH2-mutant glioma. Presented at the SNO Annual Meeting. November 19 - 23, 2025; Honolulu, Hawaii. Abstract CTNI-34.