Abstract A017-PR013: Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: An update from the iMATRIX alectinib phase I/II open-label, multi-center study
Notice bibliographique
Résumé
Abstract Background: Alectinib is a next generation, oral, ALK inhibitor being investigated in children and adolescents with ALK-fusion bearing tumors. Here we present updated safety and efficacy data from iMATRIX Alectinib phase I-II study (NCT04774718). Methods: Patients, less than 18 years of age, with ALK fusion-positive CNS and non-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 study drug pharmacokinetics. Alectinib was administered as an oral tablet or suspension twice a day according to initial weight. Investigators reported Best Overall Response according to RANO (CNS tumors) or RECIST v1.1 (solid tumors) criteria (data cut off February 2025). Results: In total 25 patients with a median age of 7.5 years (range 0-17 years) were enrolled. Fifteen patients were diagnosed with solid tumors: inflammatory myofibroblastic tumor (n = 10), renal cell carcinoma (n = 2), mesothelioma (n = 1), nephroblastoma (n = 1), and atypical melanocytic tumor (n = 1). Eight patients were diagnosed with CNS tumors: high grade glioma (n = 7) and pleomorphic xanthoastrocytoma (n = 1). Two patients had ineligible conditions: histiocytosis (n = 1) and anaplastic large cell lymphoma (n = 1). Ten of 25 patients had received prior systemic therapy. ALK fusion partners were EML4 and CLTC in 3 patients, TPM3, KIF5C, PPP1CB and FN1 in 2 patients, and DCTN1, KIF5B, NPM, STRN, CLIP1, RANBP2, ZEB2, PLEKHA7, CDC42BPB, HNRNPA3, and ZNF397 in 1 patient each. In the 24 safety evaluable patients, only 1 Dose Limiting Toxicity (DLT) of Grade 3 increased alanine aminotransferase, during multiple viral infections, was reported. The DLT resolved after treatment interruption and Alectinib was successfully tolerated at a reduced dose level. Twenty patients (83%) experienced at least one Adverse Event (AE) reported as related to Alectinib, mostly Grade 1 or 2. Grade ≥ 3 AEs assessed as related to alectinib by the investigator were reported for 6 patients (25%) and consisted of increases in CPK,AST, ALT, bilirubin; neutropenia, optic neuropathy, encephalopathy and weight gain. Of these the increased ALT (DLT) and optic neuropathy/ encephalopathy in 2 patients were serious AEs. No new safety signals were detected. Investigator reported Best Overall Response rate in 19 patients was 89.5%; (3 CRs, 14 PRs) and 2 patients were reported to have confirmed stable disease. One complete response and 5 partial responses were observed in 6/6 evaluable patients with CNS tumors. Two complete responses and 9 partial responses were seen in 11 evaluable patients with solid tumours. Four 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). Conclusions: Alectinib continues to have a favourable safety profile in pediatric patients. Clinical efficacy results are highly encouraging with most patients experiencing a tumor response. Citation Format: Francois Doz, Michela Casanova, Kyung-Nam Koh, Karsten Nysom, Adela Canete, Hyoung Jin Kang, Matthias Karajannis, Darren Hargrave, Nadege Corradini, Yeming Wu, Huanmin Wang, David Ziegler, Nicolas Prud'homme, Carla Manzitti, Quentin Campbell-Hewson, Carolina Sturm-Pellanda, Tao Xu, Dhruvitkumar S. Sutaria, Livingstone Fultang, Clare Devlin, Francis Mussai, Amar J Gajjar. Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: An update from the iMATRIX alectinib phase I/II open-label, multi-center study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr A017-PR013.
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 | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 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 ».