INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLINDED, PHASE 3 STUDY OF VORASIDENIB VERSUS PLACEBO IN PATIENTS WITH RESIDUAL OR RECURRENT GRADE 2 GLIOMA WITH AN IDH1/2 MUTATION
Bibliographic record
Abstract
Abstract AIMS Current treatments grade 2 gliomas are not curative and can be associated with short- and long-term toxicities. Vorasidenib (VOR), an oral, brain-penetrant, dual inhibitor of mutant (m)IDH1/2 enzymes, has shown a tolerable safety profile and preliminary clinical activity in phase 1 studies. METHOD In the phase 3 INDIGO study (NCT04164901), patients (pts) were randomized 1:1 to receive VOR 40 mg daily or placebo (PBO) daily in 28-day cycles. Patients were stratified by 1p19q status and baseline tumor size. Key eligibility criteria included: age ≥12; KPS >80; residual or recurrent grade 2 IDH1m or IDH2m oligodendroglioma or astrocytoma; measurable non-enhancing disease; no prior treatment for glioma with most recent surgery 1-5 years from randomization; and not in immediate need of chemotherapy/radiation. Primary endpoint: radiographic progression-free survival (PFS) by blinded independent radiology committee (BIRC). Key secondary endpoint: time to next intervention (TTNI). RESULTS As of 06 Sep2022, 331 pts were randomized across 10 countries: 168 to VOR and 163 to PBO. Median PFS by BIRC was 27.7 mos with VOR and 11.1 with PBO (HR, 0.39; 95% CI, 0.27, 0.56; 1-sided P=0.000000067). Median TTNI was not reached with VOR and 17.8 mos with PBO (HR, 0.26; 95% CI, 0.15, 0.43; 1-sided P=0.000000019). All-grade adverse events (AEs) occurring in >20% pts receiving VOR vs PBO were alanine aminotransferase increased, COVID-19, fatigue, aspartate aminotransferase increase, headache, diarrhea, nausea. Common grade ≥3 AEs (>5%): ALT increased (9.6% vs 0%). CONCLUSIONS VOR significantly improved PFS by BIRC versus PBO with a manageable safety profile. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".