Work

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

Year: 2026

Type: article

Abstract: ABSTRACT This study evaluated the safety, pharmacokinetics (PK), and efficacy of unecritinib, a novel ROS1/anaplastic lymphoma kinase (ALK)/c‐MET inhibitor, in pediatric patients with relapsed/refractory (R/R) ALK‐positive (ALK+) anaplastic large‐cell lymphoma (ALCL). This was an open‐label, single‐arm, Phase I study using a 3+3 dose‐escalation design in patients aged 10–18 years. The primary endpoints were safety, determination of the recommended phase II dose (RP2D), and PK profiling. Secondary endpoints included overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Nine patients were evaluable for toxicity and efficacy analyses. No dose‐limiting toxicities were observed. The most frequent treatment‐related adverse events were neutropenia, leukopenia, vomiting, and nausea, predominantly Grade 1–2. PK analysis showed rapid metabolism of unecritinib by carboxylesterase to its active metabolite unecritinib M, with a T max of approximately 3 h. The ORR was 100% (six complete and three partial responses). The 3‐year PFS and OS rates were 53.3% and 100%, respectively. Genomic alterations in TP53 , MYC , KMT2D , and MYCL1 were identified in a subset of patients, suggesting potential prognostic heterogeneity. Unecritinib demonstrated a favorable safety profile and promising preliminary efficacy in patients with R/R ALK+ ALCL. The RP2D was 250 mg twice daily for patients aged > 10 years. Trial Registration : ClinicalTrials.gov identifier: NCT04306887

Source: MedComm

DOI: 10.1002/mco2.71128