Abstract CT100: Safety and efficacy of AZD8853, an anti-growth and differentiation factor 15 (GDF15) antibody, in patients (pts) with advanced/metastatic solid tumors: First-in-human study
Notice bibliographique
Résumé
Abstract Background: GDF15 is overexpressed in solid tumors, with immunosuppressive effects on dendritic cells (DCs), T cells and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. AZD8853 is an IgG1 monoclonal antibody that neutralizes GDF15. This Phase 1/2a, open-label study assessed AZD8853 monotherapy in previously treated advanced/metastatic non-small-cell lung cancer, microsatellite-stable colorectal cancer (MSS-CRC) and urothelial carcinoma (UC) (NCT05397171). Methods: Eligible pts were ≥18 years old with ≥1 measurable lesion per RECIST v1.1 and ECOG PS 0/1. AZD8853 was given IV Q3W until disease progression, unacceptable toxicity or consent withdrawal. The primary objective was safety including dose-limiting toxicities (DLTs). Secondary objectives included efficacy, pharmacokinetics (PK) and pharmacodynamics (PD [free serum GDF15]). Exploratory objectives included peripheral immune PD. Results: During dose escalation, 16 pts (15 MSS-CRC, 1 UC) received AZD8853 (300 mg, n=3; 1000 mg, n=6; 3000 mg, n=7). By June 6, 2023, all pts discontinued treatment and the study. Thirteen pts (81.3%) had treatment-emergent adverse events (TEAEs; Table); the most common were diarrhea (31.3%), abdominal pain (31.3%) and decreased appetite (25%). Eight pts (50%) had Grade ≥3 TEAEs and 6 (37.5%) had serious TEAEs; none treatment-related. There were no DLTs. No pts had responses by RECIST; 5 (31.3%) had stable disease and 11 (68.8%) had disease progression as best response. AZD8853 PK was linear with a half-life of 5-10 days, supporting Q3W dosing. GDF15 suppression was transient. There was no evidence of ctDNA clearance or a dose-dependent change in peripheral immune cells including CD8+ and CD4+ T cells, DCs and MDSCs. Conclusions: AZD8853 was well tolerated. No objective responses or PD effects were seen and GDF15 suppression was not sustained, therefore no further development is planned. TABLE 1. NAND Table. AZD8853 safety AZD8853 300 mg 1000 mg 3000 mg Total Safety, n (%) N=3 N=6 N=7 N=16 TEAEs 3 (100) 4 (66.7) 6 (85.7) 13 (81.3) Grade ≥3 TEAEs 1 (33.3) 3 (50.0) 4 (57.1) 8 (50.0) TRAEs 1 (33.3) 0 2 (28.6) 3 (18.8) Grade ≥3 TRAEs 0 0 0 0 Serious TEAEs 1 (33.3) 3 (50.0) 2 (28.6) 6 (37.5) TEAEs leading to discontinuation of AZD8853 0 1 (16.7)* 0 1 (6.3) TEAEs leading to death 0 1 (16.7)* 0 1 (6.3) DLTs, n (%) N=3 N=6 N=6 † N=15 DLTs 0 0 0 0 *Death due to serious AE of cardiac arrest, unrelated to AZD8853; pt had a history of coronary artery disease, coronary stenting, and pulmonary embolism.†One pt discontinued due to clinical progression prior to completing the DLT evaluation period and was not included in the DLT-evaluable set. DLTs, dose-limiting toxicities; TEAEs, treatment-emergent adverse events, TRAEs, treatment-related adverse events Citation Format: Benedito A. Carneiro, Olumide Gbolahan, Albiruni Abdul Razak, John F. Hilton, Arthur Lambert, John Hood, Michael Pluta, Veronique Bragulat, Elhan Sanai, Rakesh Kumar, Duncan Jodrell, Patricia LoRusso. Safety and efficacy of AZD8853, an anti-growth and differentiation factor 15 (GDF15) antibody, in patients (pts) with advanced/metastatic solid tumors: First-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT100.
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 | 0,001 | 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) | 0,000 | 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 ».