Abstract B160: ANG1005: New EPiC compound for the treatment of recurrent malignant glioma
Bibliographic record
Abstract
Abstract ANG1005 is a new generation taxane created from Angiochem's Engineered Peptide Compound (EPiC) platform. Studies have shown that ANG1005 gains entry into the brain compartment by targeting the low-density lipoprotein receptor-related protein (LRP) which is one of the most highly expressed receptors on the surface of the BBB. Once inside the brain, ANG1005 enters tumor cells using the same receptor-mediated pathway through LRP, which is upregulated in various cancer cells including malignant glioma cells. Approximately 16,000 new cases of malignant glioma are diagnosed in adults in the United States every year with poor prognosis. A multi-center, phase I, open-label, sequential cohort, dose escalation study of ANG1005 in patients with recurrent malignant glioma is ongoing in the US. Study objectives include characterization of safety and tolerability and identification of maximum tolerated dose (MTD). To examine whether or not ANG1005 could be measured in malignant glioma tumors in humans, fresh, excised tumor samples from patients undergoing debulking surgery following administration of one dose of ANG1005 were collected and analyzed. ANG1005 is administered by IV infusion once every 21 days (1 treatment cycle) without premedication. Doses of 30–700 mg/m2 have been evaluated to date; 650 mg/m2 is currently being expanded as MTD. Data including adverse events and hematological parameters indicate that ANG1005 is safe and well tolerated. The most common events occurring at a severity ≥ Grade 2 according to CTCAE, version 3.0 in patients dosed ≥ 300 mg/m2 (n=28) were neutropenia (71% of patients; Grade 4 in 36%), leucopenia (61%; Grade 4 in 11%), infusion reactions (25%; mostly Grade 2 and easily controllable - no cases of Grade 4) and rash (21%; mostly Grade 2 - no cases of Grade 4); these events have been transient and manageable with standard treatments. Neurocognitive data have shown that ANG1005 does not cause cognitive impairment and tests for antibodies demonstrate that ANG1005 does not elicit antibody production even in patients who had reported infusion reactions and/or rashes. Pharmacokinetic data indicate linear ANG1005 bioavailability. Analysis of tumor samples from patients who had received doses of ANG1005 of 200–550 mg/m2 4–6 hours prior to debulking shows a concentration of ANG1005 in tumors relative to plasma of 8 to 379%. Differences between samples are attributed to the different dose levels tested, the range of timing between dosing and tumor extraction and differences in tumor consistencies. Additional analysis revealed that the tumor samples did not grow when cultured in neurospheres. Disease control (≥ stable disease) assessed by MRI was achieved in 60% of patients dosed ≥ 300 mg/m2 including one patient who was progressing on bevacizumab therapy prior to study entry. Tumor stabilization and in some cases significant reduction in tumor size and reversal of neurological deficits were observed in patients with high grade gliomas. Clinical data gathered to date indicate a promising future for the development of ANG1005 for the treatment of patients with malignant glioma. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B160.
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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) | 0.000 | 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".