Vorasidenib Demonstrates Favorable Safety Profile and Disease Stability in High-Grade IDH-Mutant Gliomas

Vorasidenib (Vorangio) was found to be well tolerated and generated disease stability in patients with grade 3 or 4 IDH-mutant gliomas who would not have been eligible for enrollment in the phase 3 INDIGO trial (NCT04164901), according to short-term retrospective data presented at the 2025 Society for Neuro-Oncology Annual Meeting.

Based on findings from the 9-month retrospective review, 53.1% (n = 32) of patients achieved stable disease, and the median treatment duration was 3.5 months. Additionally, more than half of this patient cohort remained on therapy at last follow-up, with 19 patients continuing vorasidenib.

“Overall, we saw that vorasidenib was well tolerated and provided disease stability in approximately half of our patients over a median treatment duration of 3.5 months,” said study presenter Amanda Knott, PharmD, BCPS, noting that these initial outcomes show early signals of tolerability for those with IDH-mutant high-grade gliomas.

Knott is the assistant program director of Investigational Drug Services, where she is also an instructor in pharmacy, as well as a research pharmacist at Mayo Clinic College of Medicine & Science in Rochester, Minnesota.

Patient Demographics, Prior Treatments, and Treatment Duration With Vorasidenib in Grade 3 and 4 IDH-Mutant Gliomas

The research included 32 patients with a median age of 39.5 years. The cohort consisted of 17 males (53.1%) and 15 females (46.9%), and the tumor subtypes reflected the distribution of IDH-mutant high-grade gliomas: grade 3 astrocytoma in 13 patients (40.6%), grade 3 oligodendroglioma in 11 patients (34.4%), and grade 4 astrocytoma in eight patients (25%). Additionally, contrast enhancement was present in 30 cases, whereas two patients had non-enhancing tumors at baseline.

Most individuals were heavily pretreated. Surgical resection was the most common prior modality (n = 30), followed by radiation (28) and cytotoxic chemotherapy (25). Additional systemic therapies included ivosidenib (Tibsovo) in 8 patients, bevacizumab (Avastin) in 5 patients, and pembrolizumab (Keytruda) in 3 patients. Four patients began vorasidenib with no history of prior systemic therapy.

The median treatment duration was 3.5 months (101.5 days), with a range of 18 to 255 days. Nearly 60% of patients remained on vorasidenib at last follow-up, suggesting early clinical benefit or continued disease stability.

Safety Profile and Adverse Effects (AEs) With Vorasidenib in Grade 3 and Grade 4 IDH-Mutant Gliomas

Vorasidenib demonstrated a favorable safety profile that aligned with expected toxicities. Laboratory abnormalities were predominantly low grade. Transaminitis occurred in 12 patients, all grade 1, and no high-grade liver enzyme elevations were observed. Lymphopenia developed in two individuals, both of whom previously received multiple alkylating agents. No additional hematologic toxicities were identified.

Non-laboratory AEs included fatigue, which was seen in 9 patients, headache in 4 patients, decreased appetite in 2 patients, nausea in 2 patients, and myalgias in 1 patient. One case of myalgias led to treatment discontinuation, representing the only therapy-limiting toxicity reported in the cohort.

Dr. Knott described the overall AE profile as “as expected,” reiterating that vorasidenib was “well tolerated.”

However, progression occurred in 34.4% of patients. Notably, two patients have not yet reached their first disease assessment, and two patients died during the observation period

Ongoing Prospective Studies Will Clarify Durability, Long-Term Safety, and Clinical Integration of Vorasidenib

Knott concluded the presentation by stating that: “Our conclusions are somewhat limited based on the short term follow up, so longer-term follow up is needed, and prospective studies are ongoing for vorasidenib.”

She emphasized the need for extended observation to better characterize durability of response and long-term tolerability of vorasidenib for both grade 3 and grade 4 IDH-mutant gliomas.

Reference

Knott A, Schultz S, Breen WG, et al. Experience with vorasidenib in patients with grade 3 or 4 IDH-mutant gliomas. Presented at 2025 Society of Neuro-Oncology Annual Meeting; November 19-23, 2025; Honolulu, HI. Abstract NCOG-44.