Phase 2 study of bizaxofusp, an IL-4R targeted toxin payload, in nonresectable recurrent GBM: Comparison of overall survival with contemporaneous eligibility-matched and propensity score balanced external control arm.
Notice bibliographique
Résumé
2079 Background: Bizaxofusp (MDNA55) is designed to selectively deliver a potent toxin payload to tumor cells by targeting the IL-4 receptor (IL-4R) overexpressed by GBM, but not normal brain. Localized delivery of bizaxofusp minimizes risk of off-target toxicities and systemic exposure while eliciting effective tumor cell killing. Bizaxofusp was evaluated using convection-enhanced delivery in MDNA55-05 (NCT02858895), a single-arm, open-label, multi-center Ph2 study in nonresectable recurrent GBM (rGBM). Methods: The study population comprised of de novo IDH wild-type GBM patients with 1 st or 2 nd relapse that were non-resectable. Forty-four patients were administered a single treatment of bizaxofusp (range: 18-240 μg). The primary endpoint was OS; secondary endpoints were safety and tumor response. IL-4R expression in tumor biopsies was determined using a validated assay. OS was compared to an eligibility matched external control arm (emECA) of 81 contemporaneous rGBM subjects receiving standard of care. The emECA was further refined by propensity-score balancing (pbECA) to the bizaxofusp arm based on known prognostic factors, resulting in a weighted sample size of 40.8. OS was defined as time from relapse (to unify index date in both arms) or treatment start (for analysis of tumor response) to death/censor. Tumor response was assessed following RANO and mRANO criteria. Results: Bizaxofusp showed an acceptable safety profile at doses up to 240 μg. TRAEs were primarily neurological or aggravation of pre-existing neurological deficits associated with GBM and were manageable with standard measures. Results showed that IL-4R expression did not impact mOS except in patients receiving low doses of bizaxofusp. The bizaxofusp arm had significantly longer median OS (mOS) than contemporaneous emECA (12.4 vs 7.7 months; HR: 0.64, 95% CI 0.46-0.93; p = 0.02). Survival benefit was also evident when compared to the pbECA: (12.4 vs 7.2 months; HR: 0.72, 95% CI 0.46-1.1; p = 0.27). Patients with tumor control (SD or PR/CR, n=21) had significantly longer mOS than patients with tumor progression (n=23) (16.7 vs 8.5 months; HR = 0.5, 95% CI 0.27-0.9; p = 0.01). Among patients with tumor control who had pseudoprogression (PsP) per mRANO, mOS (22.8 months) was significantly longer than patients with tumor progression (HR: 0.49, 95% CI 0.25-0.98; p = 0.049). Conclusions: Bizaxofusp achieved significant OS benefit in patients with nonresectable rGBM compared to contemporaneous emECA. Patients who experienced tumor control, including those with PsP, showed significantly longer survival than patients with tumor progression. Phase 3 ready registrational trial will comprise a high dose bizaxofusp arm and a hybrid control arm with 1/3 randomized subjects and 2/3 pmECA. Clinical trial information: NCT02858895 .
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 | 0,005 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 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 | 0,002 |
| 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 ».