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.
Bibliographic record
Abstract
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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".