Multicenter phase 2 study of alectinib in pediatric and adult patients with ALK-altered advanced solid tumors

ALK alterations occur in a range of rare malignancies; however, prospective evidence supporting alectinib beyond lung cancer remains limited. The multicenter phase 2 TACKLE trial in Japan evaluated activity and safety of alectinib (capsule or suspension) in patients with advanced ALK-altered solid tumors. The primary endpoint was centrally confirmed objective response rate (ORR) evaluated using a Bayesian design (expected ORR 40%; threshold 10%) in patients receiving intact capsules (cohort A). Twenty-six patients (age 8 months-78 years) with 11 tumor types were enrolled. ALK alterations included fusions/rearrangements (n=19), mutations (n=5), and amplifications (n=2). The median follow-up was 15 months. In cohort A (n=16 with measurable disease), the centrally reviewed ORR was 43.8%, meeting the primary endpoint. Among evaluable patients (n=24), the ORR was 54.2% and the disease control rate (DCR) was 75%. The median progression free survival was 24.9 months, and the median overall survival was 38.8 months. Patients with ALK fusions/rearrangements had ORR 76.5% and DCR 88.2%. Patients aged ≤ 15 years (n=11) had ORR 63.6% and DCR 100%. Grade ≥3 treatment-related adverse events occurred in 15.4%, with no treatment-related deaths. The authors conclude that alectinib demonstrated meaningful, durable responses with acceptable safety across ALK-altered solid tumors, particularly in patients with ALK fusions.