 mutations occur in most low-grade diffuse gliomas.

 hotspot mutations occur in various cancers, including diffuse gliomas.

Vorasidenib is an oral inhibitor of mutant 

 specifically designed for brain penetrance.

Vorasidenib reduced tumor 2-HG by >90% in resected grade 2/3 non-enhancing diffuse glioma.

Patients enrolled were ≥ 12 years of age with 

-mutated grade 2 oligodendroglioma or astrocytoma per WHO 2016 guidelines with prior surgery.

Patients had measurable non-enhancing disease (≥1 target lesion measuring ≥1 cm x ≥1 cm), confirmed by blinded review.

Patients were not in need of immediate chemotherapy or radiotherapy per investigator assessment.

Patients were given 40 mg of vorasidenib orally once daily for 28-day cycles vs placebo.

Centrally confirmed progressive disease permitted unblinding and crossover.

Primary end point was progression-free survival [PFS].

Key secondary end point was time from randomization to the initiation of first subsequent anticancer therapy or death because of any cause.

Estimated median PFS was 27.7 months for vorasidenib and 11.1 months for placebo, with a hazard ratio of 0.39.

Time to next intervention [TTNI] was 17.8 months for placebo and wasn’t reached in the vorasidenib arm.

At 24 months, an estimated 83.4% of patients in the vorasidenib arm had not initiated another therapy vs 27.0% of patients in the placebo arm.

Liver function tests showed increased ALT and AST present in vorasidenib arm and not in placebo.

Other adverse effects were fairly even matched throughout the study.

No fatal treatment emergent adverse events

At preplanned interim analysis, vorasidenib demonstrated a significant improvement in:

PFS per BIRC
(HR 0.39, 95% CI 0.27–0.56; P=0.000000067)

TTNI
(HR 0.26, 95% CI 0.15–0.43; P=0.000000019)

 mutations are not curable with current therapies and infiltrate the brain in the absence of treatment.

Vorasidenib is an oral inhibitor of the mutant IDH1/2 enzymes with proven brain penetrance.

Treatment with vorasidenib significantly improved imaging-based PFS and TTNI with a manageable safety profile in patients who were not in need of immediate chemotherapy or radiotherapy​.

Mellinghoff IK, van den Bent MJ, Blumenthal DT et al. INDIGO: a Phase 3 global, randomized, double-blinded study of vorasidenib versus placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. Abstract presented at: 2023 ASCO Annual Meeting, June 2-6, 2023.

Funding supported by Servier Pharmaceuticals. Content independently developed by OncLive.

Videos

Timothy Cloughesy, MD, reviews data from the phase 3 INDIGO trial investigating vorasidenib in patients with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation.

INDIGO: A Phase 3 Global, Randomized, Double-Blinded Study of Vorasidenib vs Placebo in Patients with Residual or Recurrent Grade 2 Glioma with an IDH1/2 Mutation

Timothy Cloughesy, MD

Articles

INDIGO: A Phase 3 Global, Randomized, Double-Blinded Study of Vorasidenib vs Placebo in Patients with Residual or Recurrent Grade 2 Glioma with an IDH1/2 Mutation