VAL-083 is effective in patients with newly-diagnosed MGMT-unmethylated glioblastoma: report of phase II study
Bibliographic record
Abstract
PURPOSE: Unmethylated MGMT is a validated biomarker for temozolomide (TMZ) resistance and poor prognosis in glioblastoma. VAL-083 (dianhydrogalactitol; DAG) is a DNA-targeting agent that forms interstrand crosslinks at O6/N7-guanine, inducing double-strand breaks and cell death independently of MGMT-mediated DNA repair. This study aimed to evaluate whether first-line VAL-083 combined with radiotherapy improves efficacy compared to standard-of-care TMZ plus radiotherapy in newly diagnosed MGMT-unmethylated GBM patients. METHODS: VAL-083 was administered intravenously on days 1-3 of a 21-day cycle, starting on day 1 of radiotherapy, with a second 3-day cycle on days 22-24 of radiotherapy. After completing the 6-week radiotherapy regimen, patients began adjuvant maintenance therapy with VAL-083 alone, administered IV at the same dose and regimen (Cycles 3-10), for up to 8 maintenance cycles. RESULTS: /day VAL-083, 15/25 (60%) had died by the censor date, with a median survival of 18.0 months. Pharmacokinetics exhibited dose-linearity. CSF levels at 2 h post-infusion were comparable to or exceeded plasma levels. Common adverse events included thrombocytopenia and neutropenia. CONCLUSIONS: /day) combined with radiation therapy was generally safe and well tolerated. Adverse events aligned with previous studies. This regimen, compared to standard-of-care TMZ, showed potential benefits in terms of disease progression and overall survival. Trial registration ClinicalTrials.gov ID NCT03050736, dated: February 13, 2017.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".