Abstract B160: ANG1005: New EPiC compound for the treatment of recurrent malignant glioma
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».