Efficacy and Safety of Alectinib in Pediatric and Adult Patients with ALK-Altered Advanced Solid Tumors: a phase II TACKLE Trial (NCCH1712/MK003).
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PURPOSE: Anaplastic lymphoma kinase (ALK) alterations occur in a range of rare malignancies; however, prospective evidence supporting alectinib beyond lung cancer remains limited. We evaluated the activity and safety of alectinib in patients with advanced ALK-altered solid tumors. PATIENTS AND METHODS: In this open-label, multicenter phase II study, patients with advanced ALK-altered solid tumors received alectinib (capsule or suspension). The primary endpoint was centrally confirmed objective response rate (ORR) per RECIST v1.1, evaluated using a Bayesian design (expected ORR: 40%; threshold: 10%) in patients receiving intact capsules (Cohort A). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-six patients (age 8 months-78 years) with 11 tumor types were enrolled; inflammatory myofibroblastic tumor (IMT) (n=9), and neuroblastoma (n=5) were most common. ALK alterations included fusions/rearrangements (n=19), mutations (n=5), and amplifications (n=2). Median follow-up was 15.0 months. In Cohort A (n=16 with measurable disease), centrally reviewed ORR was 43.8%, meeting the primary endpoint. Among evaluable patients (n=24), ORR was 54.2% and DCR was 75.0%. Median PFS and OS were 24.9 and 38.8 months. Patients with ALK fusions/rearrangements (n=17) had ORR and DCR of 76.5% and 88.2%. All patients with IMT achieved tumor shrinkage (ORR 87.5%). Patients ≤15 years (n=11) had ORR and DCR of 63.6% and 100%, respectively. Grade ≥3 treatment-related adverse events occurred in 15.4% (n=4), with no treatment-related deaths. CONCLUSIONS: Alectinib demonstrated meaningful, durable responses with acceptable safety across ALK-altered solid tumors, particularly in patients with ALK fusions, supporting further tumor-agnostic development.