Table of Contents

• Trial overview
• Who can join the studies
• Trial phases and study design
• What the trials measure
• Key studies of Vorasidenib
• Patient-focused terms

Trial overview

These studies are looking at Vorasidenib in people with specific IDH1 or IDH2 mutated brain tumors.^[1] The trials focus on glioma and astrocytoma, including lower-grade and higher-grade disease, and they are designed to test whether the treatment can delay tumor growth and how safe it is.^[1][2]

All of the trials listed are interventional studies, which means the researchers give a treatment and then measure the results.^{[1][2][3] The studies include two Phase 3 trials and one Phase 1 trial.[1][2][3]}

Who can join the studies

Each trial has a different target group, but all are based on tumor type and mutation status.^{[1][2][3] In one study, people must have residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation and must have had surgery as their only treatment.[1]}

Another Phase 3 study includes people with IDH-mutant grade 2 or 3 astrocytoma after first-line chemoradiotherapy, which means after a first round of chemotherapy and radiation treatment.^[2] The Phase 1 study includes participants with IDH1- or IDH2-mutant glioma and tests Vorasidenib together with temozolomide.^[3]

Trial phases and study design

The two Phase 3 studies are larger trials meant to test whether Vorasidenib works better than placebo in the chosen patient groups.^{[1][2] A placebo is a look-alike treatment without active medicine, used so the results can be compared fairly.[1][2]}

The Phase 1 study is smaller and focuses first on safety and tolerability, which means how well people can take the treatment and what side effects happen.^[3] It also explores early signs that the combination with temozolomide may help control the disease.^[3]

What the trials measure

The main outcome in the first Phase 3 study is radiographic progression-free survival, measured by a blinded review committee using modified RANO-LGG criteria.^[1] This means the researchers use scans to see how long the tumor does not get worse.^[1]

The second Phase 3 study measures progression-free survival from the date of enrollment using RANO 2.0 criteria.^[2] The goal is to show that Vorasidenib maintenance therapy can improve the time before the disease gets worse compared with placebo.^[2]

The Phase 1 study measures dose-limiting toxicities in the Phase 1b part, along with the incidence and severity of adverse events, serious adverse events, and adverse events of special interest.^[3] It also looks at progression-free survival status at 12 months and early clinical efficacy in the group treated at the recommended dose.^[3]

Key studies of Vorasidenib

NCT04164901 is a Phase 3 study in residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation.^[1] Its main goal is to show that Vorasidenib improves radiographic progression-free survival compared with placebo in people who had surgery as their only prior treatment.^[1]

NCT06809322 is a Phase 3 study in IDH-mutant grade 2 or 3 astrocytoma after standard chemoradiotherapy.^[2] It studies Vorasidenib as maintenance therapy and compares it with placebo to see whether it improves progression-free survival.^[2]

NCT06478212 is a Phase 1 multicenter study of Vorasidenib with temozolomide in participants with IDH1- or IDH2-mutant glioma.^[3] This study is mainly about safety, tolerability, and early signs of benefit, and it also includes a 12-month progression-free survival check.^[3]

Patient-focused terms

Progression-free survival means the time during which the tumor does not grow or get worse.^{[1][2][3] Adverse events are unwanted medical problems that happen during a study, and serious adverse events are the more severe ones.[3]}

Recommended dose means the dose chosen for later study after safety testing.^[3] Multicenter means the study is run at more than one hospital or clinic.^[3]