Abstract CT039: Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101)
Notice bibliographique
Résumé
Abstract Background: Systemic delivery of IL-12 is limited by significant toxicity. To achieve therapeutic doses without toxicity, IL-12 was conjugated to aluminum hydroxide (ANK-101) and a Phase I clinical trial was conducted to determine safety, PK, and biologic activity in patients with advanced solid accessible tumors. Methods: A modified dose-escalation Phase 1 study was conducted (NCT06171750) in patients with accessible, advanced solid tumors progressing following standard therapy. ANK-101 was administered at escalating doses with volume adjusted based on tumor diameter. Adverse events were reported per NCI CTCAE, version 5. Serum was collected at specified cycles for pharmacokinetic (PK), interferon-γ (IFN-γ), serum cytokines, and anti-drug antibody (ADA) titers. Whole blood was obtained for peripheral immune cell analysis by flow cytometry. Serial tumor biopsies were obtained for PD-L1 expression, immune cell characterization by IHC and gene expression was evaluated by Nanostring. Tumor measurements were performed every 12 weeks. Statistical analysis was primarily descriptive with categorical variables summarized with numbers and percentages while continuous variables were calculated as mean, standard deviation, median, and range. P≤ 0.05 was considered significant. Results: 15 pts were enrolled (median age: 68 years). 60% were female and 60% had baseline ECOG score of 0. Notably, 73.3% of those enrolled had received > 3 lines of prior therapy. Seven patients had melanoma, 4 had squamous cell cancer of the head and neck, 2 had breast cancer, and 1 each had bladder and apocrine adenocarcinoma. No patients experienced drug-limiting toxicity while on study and no patients discontinued study treatment due to an adverse event. There were no ≥ Grade 3 treatment-related adverse events. There were two Grade 1 CRS-related fevers. PK analysis showed a trend towards dose response but demonstrated overall low systemic exposures of ANK-101. ADA were detected in one patient treated after three cycles. Biologic activity was further confirmed by an increase in serum IFN-γ with peak levels ranging 18-496 pg/mL 24 hrs after treatment. ANK-101 induced local expression of PD-L1 and recruitment of CD8+ T cells and increased local gene expression consistent with immune activation. To date, 11 subjects are evaluable for response with a disease control rate of 63.6% and best objective responses include 1 PR, 7 SD, and 3 PD. 6 subjects remain on active treatment. Conclusions: ANK-101 is well tolerated at doses tested, demonstrated biologic activity, and was associated with durable disease control across different tumors in a heavily pretreated population. Further investigation is warranted. Citation Format: Jong Chul Park, Brendan Curti, Marcus O. Butler, Gail Iodice, Sailaja Battula, Joseph Elassal, James L. Gulley, Jeffery Schlom, Howard L. Kaufman, John M. Kirkwood. Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT039.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,002 |
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 source (Gemma direct ou Codex distillé), 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 ».