ACTR-71. FULL ENROLLMENT RESULTS FROM THE PHASE 1/2, MULTICENTER, OPEN-LABEL STUDY OF MARIZOMIB (MRZ) ± BEVACIZUMAB (BEV) IN RECURRENT WHO GRADE IV MALIGNANT GLIOMA (GLIOBLASTOMA, RGBM)
Bibliographic record
Abstract
MRZ – an irreversible, brain-penetrant, pan-proteasome inhibitor with anti-glioma preclinical activity – was evaluated in BEV-naïve rGBM patients. Phase 1 (P1) MRZ+BEV, 3 + 3 MRZ dose-escalation (N=6, 3, 3 at 0.55, 0.7, 0.8 mg/m2) followed by dose-expansion (N=24, 0.8 mg/m2). Phase 2 (P2) MRZ monotherapy (N=30, 0.8 mg/m2). Treatments (IV, 28-day (D) cycles): MRZ (10min infusion) D1, 8, 15; BEV (10 mg/kg) D1, 15. Tumor response (RANO criteria) every other cycle; MRZ and BEV PK, and proteasome inhibition in blood evaluated in P1. as of 14Apr2017: P1 mean age 55 yrs, 64% male, mean treatment duration 5.3 cycles, 1 patient active; P2 56 yrs, 57% male, 2.5 cycles, 6 patients active. One DLT (fatigue) in P1 at 0.55 mg/m2, no other DLTs. P1 treatment-related AEs (TRAEs Grade ≥3 in ≥2 patients): hypertension, headache, confusional state, fatigue, hallucination, proteinuria; three Grade 4 SAEs (appendicitis perforated, depressed level of consciousness, not-related; blindness, BEV-related), three Grade 5 SAEs (2 PD, not-related; intracranial hemorrhage, BEV-related). P2 TRAEs (Grade ≥3 in ≥2 patients): fatigue, hallucination, lethargy; one Grade 4 SAE (hallucination). P1 overall response (≥PR) 44% (16/36) including 1 CR, 15 PR; overall survival (OS) at 6/9/12 months (mos) 75/60/39%, median 9.4mos; OS 68/45/15% (median 7.2mos) in unmethylated MGMT (uMGMT, N=22), 78/78/67% (median not reached) in methylated MGMT (N=10). In P2: 1 PR, 6 SD; 4 patients (3 SD, 1 PR) ongoing at 5–10 cycles. P1 patients experiencing ≥1 CNS-related AEs (any grade: ataxia/balance disorder/dizziness/dysarthria/fall/gait disturbance/hallucination) have increased OS (83/74/45%, median 11.4mos, N=23) versus patients without these AEs (59/34/25%, median 6.3mos, N=13). MRZ monotherapy and MRZ+BEV active in rGBM overall and in uMGMT. Possible therapeutic improvement in patients experiencing CNS AEs will be explored in ongoing P2 MRZ+BEV extension allowing intra-patient MRZ dose-escalation if no CNS AE in first cycle (0.8 mg/m2).
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".