INDIGO was a phase 3, randomized, multicenter, double-blind, placebo-controlled trial (N=331)1,2
were required to:
- Be ≥12 years of age
- Have Grade 2 IDH1- or IDH2-mutant astrocytoma or oligodendrogliomaa
- Have prior surgery for glioma
- Have measurable, non-enhancing disease
- Have not received prior anticancer treatment, including chemotherapy or radiotherapy
In the INDIGO study, patients who were randomized to placebo were allowed to cross over to receive VORANIGO after documented radiographic disease progression.1
The INDIGO study was unblinded on March 7, 2023, at which point patients were offered the opportunity to cross over from placebo to take VORANIGO at investigator discretion.3
Treatment continued until radiographic disease progression or unacceptable toxicity.1
Tumor assessments were performed every 12 weeks.1
aIDH1 or IDH2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test.1
bRandomization was stratified by local 1p/19q status (codeleted or not codeleted) and baseline tumor size (diameter ≥2 cm or <2 cm).1
INDIGO trial efficacy outcomes
Following the primary analysis data cutoff of September 6, 2022, the extended analysis includes 6 months of additional data to the date of unblinding on March 7, 2023.3
The extended analysis for progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), and seizure activity was not controlled for multiplicity.
Major efficacy outcome: PFS
The time from randomization to the date of the first documented disease progression or death due to any cause.2,c
See VORANIGO PFS results
Key secondary outcome: TTNI
The time from randomization to the initiation of the first subsequent anticancer therapy or death due to any cause.1
See VORANIGO TTNI results
Other secondary outcome: TGR
The on-treatment percentage change in tumor volume every 6 months.2
See VORANIGO TGR results
Exploratory outcome: Seizure activity
The number and severity of seizures were self-reported by patients using a diary during each cycle.3
See VORANIGO seizure activity resultscPFS was evaluated by a blinded independent review committee (BIRC) per modified Response Assessment in Neuro-Oncology for Low Grade Glioma (RANO-LGG) criteria.1 The RANO criteria for LGGs define progressive disease as either a radiographic disease progression (a ≥25% increase in the sum of the products of perpendicular T2-weighted or T2-weighted fluid-attenuated inversion recovery), or the presence of a new lesion as a newly measurable or increased enhancement.2
INDIGO patient characteristics
The study population was generally balanced across treatment arms, including age, histologic subtype, and type of surgery2,4
More than 50% of patients treated with VORANIGO had gross total resection at the time of surgery
| Demographic and disease characteristics | VORANIGO (n=168) |
Placebo (n=163) |
|---|---|---|
| Demographics | ||
| Age | ||
| Median years (range) | 40.5 (21-71) | 39 (16-65) |
| Age distribution, % | ||
| 16 or 17 years | 0 | 0.6 |
| 18 to 39 years | 45 | 53 |
| 40 to 64 years | 54 | 45 |
| ≥65 years | 1.2 | 0.6 |
| Male sex, % | 60 | 53 |
| Disease characteristics | ||
| Histologic subtype, % | ||
| Oligodendroglioma (1p/19q-codeleted) | 52 | 52 |
| Astrocytoma (1p/19q-non-codeleted) | 48 | 49 |
| Number of previous surgeries for glioma, % | ||
| 1 | 75 | 82 |
| ≥2 | 25 | 18 |
| Surgery type,4 % | ||
| Biopsy | 14 | 12 |
| Sub-total resection | 48 | 41 |
| Gross total resection | 51 | 58 |
| IDH mutation status, % | ||
| IDH1-positived | 97 | 93 |
| R132H | 87 | 85 |
| R132C | 4.8 | 4.3 |
| R132G | 3.0 | 0.6 |
| R132L | 1.2 | 2.5 |
| R132S | 1.2 | 1.2 |
| IDH2-positive | 3.0 | 7 |
| R172K | 1.8 | 6 |
| R172G | 1.2 | 0 |
| R172W | 0 | 0.6 |
dTwo patients in the placebo group had CDKN2A homozygous deletion.2
