PB1820: CD47-BLOCKER TTI-622 COMBINED WITH AZACITIDINE IN PATIENTS WITH TP53-MUTATED ACUTE MYELOID LEUKEMIA (AML) AND WITH AZACITIDINE + VENETOCLAX IN ELDERLY OR UNFIT PATIENTS WITH TP53-WILDTYPE AML
Notice bibliographique
Résumé
Background: CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a “don’t eat me” signal to suppress macrophage phagocytosis. TTI-622 is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4. It is designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc. Importantly, unlike many CD47-blocking agents, TTI-622 does not bind to human red blood cells. Increased expression of CD47 is an adverse prognostic factor in acute myeloid leukemia (AML) due to its association with reduced event-free and overall survival, and blockade of CD47 has shown pre-clinical and clinical activity in AML. In vitro, both azacitidine and venetoclax significantly enhanced the pro-phagocytic effect of TTI-622 on macrophages. Aims: To characterize the safety and preliminary efficacy profile of TTI-622 in combination with azacitidine in newly diagnosed TP53-mutated AML and in combination with azacitidine + venetoclax in elderly or unfit, newly diagnosed TP53-wildtype AML. Pharmacokinetics and immunogenicity of TTI-622 combined with azacitidine ± venetoclax will also be investigated. Primary endpoints include dose-limiting toxicities, incidence of adverse events (AEs) and complete response (CR). Minimal residual disease status will also be evaluated. Methods: As part of an ongoing dose-escalation and expansion trial of TTI-622 (NCT03530683), patients with AML meeting the below key entry criterion are enrolled. Cohort A includes patients with newly diagnosed TP53-mutated AML. Cohort B includes patients with newly diagnosed TP53-wildtype AML who are either elderly (375 years) or unfit. Unfit patients include those < 75 years with one or more of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status of 2, clinically significant heart or lung comorbidities, contraindication to anthracycline therapy, or other comorbidity the investigator regards as incompatible with intensive remission induction chemotherapy. All patients from both cohorts must have documented bone marrow or peripheral blast counts 3 20% and must have received no prior systemic therapy for AML nor hypomethylating agents for any antecedent hematologic disorders prior to transformation to AML. Patients must have no extramedullary disease or leukocytosis >25,000/mL. Renal function must be 330 mL/minute based on Cockcroft-Gault estimate. There are no restrictions based on neutrophil or platelet counts, or hemoglobin level. Patients with AML secondary to antecedent hematologic disorders or therapy induced will not comprise more than 50% of either Cohort. Up to 30 patients will be enrolled into each cohort. In 28-day cycles, patients in both Cohorts will receive TTI-622 8 mg/kg intravenous (IV) infusions weekly combined with azacitidine 75 mg/m2 administered either IV or subcutaneously for 7 consecutive days, repeated approximately every 4 weeks. Patients in Cohort B will also receive venetoclax 100 mg and 200 mg orally on Days 1 and 2, respectively, followed by 400 mg (or equivalent adjusted for azoles) daily thereafter. Safety monitoring includes clinical laboratories and assessments of AEs based on CTCAE v 4.03. Response assessments of both bone marrow and peripheral blood are performed at the end of Cycles 1, 2 and 4; and then every 3 cycles thereafter. Response assessment is per the ELN2017 criteria. Results: Results N/A (trial-in-progress) Summary/Conclusion: Conclusion N/A (trial-in-progress)
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».