Safety, Efficacy, and Pharmacokinetics of Unecritinib (TQ-B3101) in Pediatric Patients with Relapsed/Refractory Anaplastic Lymphoma Kinase Positive Anaplastic Large Cell Lymphoma: A Phase I Study

Background Over several decades, despite multiple treatment strategies for pediatric patients with anaplastic large-cell lymphoma (ALCL), approximately 30% of pediatric patients with ALCL experience relapse. This study investigated the safety and efficacy of unecritinib (TQ-B3101), a novel inhibitor of ROS1, ALK, and c-MET kinases, for the first time, in pediatric patients with relapsed/refractory (R/R) ALK+ ALCL. Methods This was an open-label, single-arm, phase I study. Eligible patients were aged 10-18 years. A 3+3 design was employed to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). The dose levels investigated were 200, 250, and 300 mg twice daily (BID). The primary end points were safety and drug pharmacokinetics. Secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results Nine patients were screened, enrolled, and evaluated for toxicity and responses. No dose-limiting toxicities occurred, and the MTD was not reached. The most frequently reported treatment-related adverse events were neutropenia, leukopenia, vomiting, and nausea, predominantly of grade 1 or 2. Most of the administered unecritinib was hydrolyzed by carboxylesterase in the body to form unecritinib M, with Tmax of approximately 3 h. The ORR was 100%, with six complete and three partial responses. The median PFS and OS have not been reached, with all patients still alive. Six patients who underwent targeted gene panel sequencing had alterations in other genes, including TP53, MYC, KMT2D, and MYCL1, indicating poor prognosis. Conclusion Unecritinib showed a good safety profile and promising efficacy in pediatric patients with R/R ALK+ ALCL. The RP2D of unecritinib is 300 mg BID for pediatric patients older than 10 years.