ATIM-03. ACT IV: AN INTERNATIONAL, DOUBLE-BLIND, PHASE 3 TRIAL OF RINDOPEPIMUT IN NEWLY DIAGNOSED, EGFRvIII-EXPRESSING GLIOBLASTOMA
Bibliographic record
Abstract
The EGFR deletion mutation, EGFRvIII, is expressed in ~30% of glioblastomas (GBM). The EGFRvIII-targeted vaccine rindopepimut consists of EGFRvIII peptide conjugated to keyhole limpet hemocyanin (KLH). A survival benefit was observed in a randomized phase 2 trial of recurrent GBM (ReACT; n=73). In three phase 2 studies of 105 total patients with newly diagnosed, EGFRvIII+ GBM and minimal residual disease (MRD), the median overall survival (mOS) was 20–22 months, as compared to ~16 months for two matched contemporary datasets (n=16, n=29). Patients with newly diagnosed, resected, EGFRvIII+ GBM were, after standard chemoradiation, stratified by RPA class, MGMT promoter methylation, and geographic region, and randomized (1:1) to double-blind rindopepimut or control (KLH) concurrent with standard maintenance temozolomide. Primary endpoint is OS for MRD patients (enhancing tumor <2 cm2 post-chemoradiation by central review) aiming to detect hazard ratio (HR) ≤0.71 with 80% power and alpha=0.05 (log-rank test). Interim analyses were preplanned at 50% and 75% of events. Secondary analyses included patients with ≥2 cm2 of residual tumor (non-MRD). 745 patients (405 MRD) were enrolled at 165 centers. The study was terminated for futility after the 2nd interim analysis (MRD OS HR=0.99). At final analysis, mOS for rindopepimut vs. control was 20.1 vs. 20.0 (HR=1.01; p=0.93) in the MRD cohort, and 14.8 vs. 14.1 (HR=0.79; p=0.066) with 2-year OS 30% vs. 19% in the non-MRD cohort. There were no substantial differences in progression-free survival. Rindopepimut was well tolerated (chief toxicity: injection site reaction) with robust anti-EGFRvIII immune response. The study failed to demonstrate a survival benefit for patients treated with rindopepimut and standard chemotherapy. Rindopepimut OS is comparable to prior studies, however, patients in the control arm fared better than historical controls. A trend for long-term survival benefit in non-MRD patients suggests a preferential effect in bulkier disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".