Abstract PR011: Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: Updated data from the iMATRIX Alectinib phase I/II open-label, multi-center study
Notice bibliographique
Résumé
Abstract Background Alectinib is a central nervous system (CNS)-penetrant, oral, inhibitor of ALK-fusion proteins that has demonstrated durable responses in adults with ALK-positive non-small cell lung cancer and children with Anaplastic Large Cell Lymphoma. In children and adolescents there remains a significant unmet clinical need for patients with tumors harboring ALK-fusions, including infantile high-grade gliomas and inflammatory myofibroblastic tumors at diagnosis or relapse. Here we present updated safety and efficacy data from the iMATRIX Alectinib phase I-II study (NCT04774718). Methods Patients with ALK fusion-positive solid or CNS tumors for whom prior treatment has proven to be ineffective or for whom there is no satisfactory treatment available, less than 18 years of age, were eligible. Patients were recruited to the Part 1, safety run-in to confirm the recommended phase 2 dose (RP2D) and monitor drug pharmacokinetics. Investigators reported Best Overall Response according to RANO (CNS tumors), RECIST (solid tumors) or INRC (neuroblastoma) criteria with a data cut off of January 2024. Results In total 16 patients with a median age of 10 years (range 0 months - 17 years), diagnosed with inflammatory myofibroblastic tumor (n=5), high grade glioma (n=5), renal cell carcinoma (n=2), mesothelioma (n=1), nephroblastoma (n=1), ALK-fusion histiocytosis (n=1, protocol deviation) and anaplastic large cell lymphoma (n=1, protocol deviation) were enrolled. Among 16 patients, 10 had not received prior systemic therapy. ALK fusion partners were EML4 in 3 patients, CLTC and KIF5C in 2 patients each, and FN1, KIF5B, NPM, PPP1CB, STRN, TPM3, PLEKHA7, DCTN1 and HNRNPA3 in 1 patient each. Only 1 Dose Limiting Toxicity of Grade 3 increased alanine aminotransferase, in the context of multiple intercurrent viral infections, was reported in an 8 year old with nephroblastoma. The DLT resolved after treatment interruption and alectinib was restarted at a reduced dose level. Thirteen patients experienced an Adverse Event (AE) reported as related to alectinib, including 5 patients with Grade ≥ 3 related AE. There were no AE-related deaths, and no new safety signals detected. Investigator reported Best Overall Response rate in 12 patients was 91.7%; (1 CR, 10 PR) and 1 patient was reported to have Stable Disease. Four patients were excluded from the efficacy analysis due to protocol deviations related to the inclusion criteria (n=2 had an ineligible tumour type, n=1 was not dosed, n=1 had no measurable disease according to RANO criteria). Conclusions Alectinib continues to be well tolerated in pediatric patients with ALK-fusion positive solid or CNS tumors. In this hard-to-treat population, efficacy results are very promising with the majority of patients experiencing a tumour response, indicating a positive benefit-risk profile. AcknowledgmentsWe acknowledge Thorsten Ruf’s contribution to the study design and implementation. 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, Carolina Sturm, Johannes Noe, Tao Xu, Nastya Kassir, Yachun Tai, Francis Mussai, Clare Devlin, Amar Gajjar. Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: Updated data from the iMATRIX Alectinib phase I/II open-label, multi-center study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr PR011.
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 | 0,002 | 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 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».