ACTR-42. CLINICAL TRIALS OF VAL-083 IN PATIENTS WITH CHEMORESISTANT GLIOBLASTOMA
Bibliographic record
Abstract
Glioblastoma (GBM) is the most common CNS-tumor. Patients with recurrent GBM have few treatment options and dismal prognosis. O6-methylguanine-DNA-methyltransferase (MGMT) is correlated with resistance to standard-of-care treatment with temozolomide and poor patient outcomes. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that readily crosses the blood-brain barrier and has demonstrated MGMT-independent activity in multiple GBM cell-lines and cancer stem cells, in vitro. VAL-083 showed promise against CNS-tumors in prior NCI-sponsored clinical trials. We recently concluded a phase I/II clinical trial studying VAL-083 in recurrent GBM after failing temozolomide and bevacizumab, suggesting potential of VAL-083 to offer clinically meaningful survival benefits and a promising new treatment for GBM patients who have failed or are unlikely to respond to currently available chemotherapeutic regimens. In this phase I/II trial, VAL-083, 40 mg/m2/day x 3 every 21 days was well tolerated and was selected for study in subsequent clinical trials in GBM. These trials include i) a pivotal, randomized Phase 3 study measuring survival outcomes compared to “physician’s choice” control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in bevacizumab-failed GBM. ii) A non-comparative, biomarker-driven, Phase 2 study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 improves overall survival at 9 months, compared to reported CCNU control in bevacizumab-naïve patients. iii) A single arm Phase 2 study to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT-levels. Trial designs and further details will be presented at the meeting. The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.006 | 0.002 |
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".