Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: A data update from the iMATRIX alectinib phase I/II open-label, multi-center study.
Notice bibliographique
Résumé
10004 Background: Alectinib is a next generation oral inhibitor of ALK-fusion proteins, being investigated in children and adolescents with ALK-fusion bearing tumors at diagnosis or relapse. Here we present updated safety and efficacy data from the iMATRIX Alectinib phase I-II study (NCT04774718). Methods: Patients, less than 18 years of age, with ALK fusion-positive solid or CNS tumors for whom prior treatment had proven to be ineffective or for whom there was no satisfactory treatment available were eligible. Patients were recruited to Part 1 to confirm the recommended phase 2 dose (RP2D) and to monitor drug pharmacokinetics. Investigators reported Best Overall Response according to RANO (CNS tumors) or RECIST v1.1 (solid tumors) criteria with a data cut off of July 2024. Results: In total 22 patients with a median age of 8 years were enrolled. Fourteen patients were diagnosed with solid tumors: inflammatory myofibroblastic tumor (n = 9), renal cell carcinoma (n = 2), mesothelioma (n = 1), nephroblastoma (n = 1), and atypical melanocytic tumor (n = 1). Six patients were diagnosed with CNS tumors: high grade glioma (n = 5) and pleomorphic xanthoastrocytoma (n = 1). Two patients had ineligible conditions: histiocytosis (n = 1) and anaplastic large cell lymphoma (n = 1). Among the 22 patients, 14 had not received prior systemic therapy. ALK fusion partners were EML4 and CLTC in 3 patients, TPM3 and KIF5C in 2 patients, and DCTN1, FN1, KIF5B, NPM, PPP1CB, STRN, CLIP1, RANBP2, ZEB2, PLEKHA7, CDC42BPB and HNRNPA3 in 1 patient each. In the 21 safety evaluable patients, only 1 DLT of Grade 3 increased alanine aminotransferase, in the context of multiple viral infections, was reported. The DLT resolved after treatment interruption and Alectinib was restarted at a reduced dose level, and then tolerated well. Eighteen patients (86%) experienced at least one Adverse Event (AE) reported as related to Alectinib, the majority being of Grade 1 and 2 severity. Grade ≥ 3 AEs related to alectinib were reported for 5 patients (23.8%) and there were 2 patients with serious AEs related to Alectinib. There were no new safety signals detected. Investigator reported Best Overall Response rate in 16 patients was 87.5%; (14 PRs) and 2 patients were reported to have stable disease. A partial response was observed in 5/5 evaluable patients with CNS tumors and in 9/11 evaluable patients with solid tumours. Six patients were excluded from the efficacy analysis due to ineligible tumor type (n = 2), not dosed (n = 1), no measurable disease according to RANO criteria (n = 1) or lack of response assessment by the analysis cut-off date (n = 2). Conclusions: Alectinib continues to have a favourable safety profile in pediatric patients. Despite this being a very challenging population to treat, clinical efficacy results are transformational with the majority of patients experiencing a tumor response. Clinical trial information: NCT04774718 .
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| 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 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 ».