INDIGO
Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO)
Phase 3N = 331NCT04164901
- Population
- Patients with residual or recurrent grade 2 IDH1- or IDH2-mutant glioma who had had no previous treatment other than surgery (follow-up report: age 12 years or older, Karnofsky performance-status score 80 or higher, at least one previous surgery); 168 assigned to vorasidenib and 163 to placebo
- Design
- Randomised, double-blind, placebo-controlled phase 3 trial: oral vorasidenib 40 mg once daily or matched placebo in 28-day cycles; crossover to vorasidenib from placebo was permitted on confirmed imaging progression; primary endpoint imaging-based progression-free survival by blinded independent review committee; key secondary endpoint time to next anticancer intervention
- Primary endpoint
- PFS
- Arms
- Vorasidenib (experimental, n = 168): Oral vorasidenib 40 mg once daily in 28-day cycles
- Placebo (control, n = 163): Matched oral placebo once daily in 28-day cycles
- People
- Mellinghoff IK, INDIGO Trial Investigators
PFSHR 0.39 (95% CI 0.27–0.56)Δ median PFS+16.6 monthsTime to next interventionHR 0.26 (95% CI 0.15–0.43)PFSHR 0.35 (95% CI 0.25–0.49)Time to next interventionHR 0.25 (95% CI 0.16–0.40)
Show the numbers
| Endpoint | Analysis | Vorasidenib | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (n=331)Imaging-based progression-free survival according to blinded independent review committee assessment | primarymedian follow-up 14.2 monthsMellinghoff 2023 | median 27.7 months | median 11.1 months | HR 0.39 (95% CI 0.27–0.56)P<0.001 |
| Time to next interventionRandomised patients (n=331)Time to the next anticancer intervention (key secondary endpoint) | primaryMellinghoff 2023 | — | — | HR 0.26 (95% CI 0.15–0.43)P<0.001The abstract prints the hazard ratio and P value but no median for either arm. |
| PFSFull analysis set (all randomly assigned patients, per the abstract)Progression-free survival per masked independent review committee, with 6 further months of double-blind data to unblinding | long term-updatemedian follow-up 20.1 monthsCloughesy 2025 | — | median 11.4 months (11.1–13.9) | HR 0.35 (95% CI 0.25–0.49)Vorasidenib arm median not reached (95% CI 22.1 to not estimated), so only the placebo median is recorded. Data from the second interim analysis (6 September 2022) to unblinding (7 March 2023). |
| Time to next interventionFull analysis set (all randomly assigned patients, per the abstract)Time to next anticancer intervention, with 6 further months of double-blind data to unblinding | long term-updateCloughesy 2025 | — | median 20.1 months (17.5–27.1) | HR 0.25 (95% CI 0.16–0.40)Vorasidenib arm median not estimated, so only the placebo median is recorded. |
| Endpoint | Analysis | Vorasidenib | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (n=331)Imaging-based progression-free survival according to blinded independent review committee assessment | primarymedian follow-up 14.2 monthsMellinghoff 2023 | median 27.7 months | median 11.1 months | HR 0.39 (95% CI 0.27–0.56)P<0.001 |
| Time to next interventionRandomised patients (n=331)Time to the next anticancer intervention (key secondary endpoint) | primaryMellinghoff 2023 | — | — | HR 0.26 (95% CI 0.15–0.43)P<0.001The abstract prints the hazard ratio and P value but no median for either arm. |
| PFSFull analysis set (all randomly assigned patients, per the abstract)Progression-free survival per masked independent review committee, with 6 further months of double-blind data to unblinding | long term-updatemedian follow-up 20.1 monthsCloughesy 2025 | — | median 11.4 months (11.1–13.9) | HR 0.35 (95% CI 0.25–0.49)Vorasidenib arm median not reached (95% CI 22.1 to not estimated), so only the placebo median is recorded. Data from the second interim analysis (6 September 2022) to unblinding (7 March 2023). |
| Time to next interventionFull analysis set (all randomly assigned patients, per the abstract)Time to next anticancer intervention, with 6 further months of double-blind data to unblinding | long term-updateCloughesy 2025 | — | median 20.1 months (17.5–27.1) | HR 0.25 (95% CI 0.16–0.40)Vorasidenib arm median not estimated, so only the placebo median is recorded. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.39 | 0.27–0.56 |
| Time to next intervention | 0.26 | 0.15–0.43 |
| PFS | 0.35 | 0.25–0.49 |
| Time to next intervention | 0.25 | 0.16–0.4 |
- Vorasidenib (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Vorasidenib | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 17 | 65.4% | 34.6% |
| 35 | 41.7% | 11.2% |
| 52 | 27.2% | 3.9% |
| 69 | 17.8% | 1.3% |
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo |
|---|---|
| 0 | 100.0% |
| 7 | 65.3% |
| 14 | 42.7% |
| 21 | 27.9% |
| 29 | 17.1% |
Appears in
Sources
Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, et al. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 2023;389(7):589-601.
Cloughesy TF, van den Bent MJ, Touat M, Blumenthal DT, Peters KB, Ellingson BM, et al. Vorasidenib in IDH1-mutant or IDH2-mutant low-grade glioma (INDIGO): secondary and exploratory endpoints from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2025;26(12):1665-1675.