INDIGO Trial Comparison Arm
The comparison arm in the INDIGO Phase 3 registration trial for vorasidenib was placebo. 1, 2
Trial Design
The INDIGO trial was a randomized, double-blind, placebo-controlled Phase 3 study that compared vorasidenib (40 mg oral daily) against matched placebo in patients with WHO Grade 2 IDH-mutant glioma 1, 2. This was a 1:1 randomization stratified by 1p/19q codeletion status and baseline tumor size 3.
Key Trial Details
Patient Population:
- Adult and pediatric patients ≥12 years old
- Grade 2 astrocytoma or oligodendroglioma with IDH1 or IDH2 mutation
- Residual or recurrent disease following surgery (biopsy, subtotal resection, or gross total resection)
- No prior anticancer treatment except surgery
- Karnofsky performance status ≥80
- Measurable non-enhancing disease (≥1 target lesion measuring ≥1 cm²)
- Appropriate candidates for watch-and-wait approach 1, 2
Study Enrollment:
- 331 total patients randomized
- 168 patients received vorasidenib
- 163 patients received placebo 2
Placebo Arm Outcomes
The placebo arm served as the control to demonstrate vorasidenib's efficacy. Key outcomes in the placebo group included:
- Median PFS: 11.1-11.4 months 1, 2
- 12-month PFS rate: 43% (570 progressions or deaths per 1,000 patients) 1
- Time to next intervention: 20.1 months 3
- Tumor growth rate: 14.4% increase every 6 months 3
- Grade ≥3 adverse events: 13.5% 2
Clinical Significance
The placebo-controlled design was critical for FDA approval, as it allowed clear demonstration of treatment effect in this rare malignancy with long natural history 4. Crossover from placebo to vorasidenib was permitted upon confirmed imaging-based disease progression 2, which was an important ethical consideration given the demonstrated efficacy at interim analysis.
The trial demonstrated a hazard ratio of 0.39 (95% CI: 0.27-0.56; P<0.001) for progression-free survival, representing a 61% reduction in risk of progression or death compared to placebo 1, 2.