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.
- 1Department of Pediatric Oncology State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center For Cancer Collaborative Innovation Center For Cancer Medicine Sun Yat-sen University Cancer Center Guangzhou People's Republic of China.
- 2Department of Medical Oncology State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center For Cancer Collaborative Innovation Center For Cancer Medicine Sun Yat-sen University Cancer Center Guangzhou People's Republic of China.
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 Tmax 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.
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BibTeX
@article{lu2026safety,
title = {{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.}},
author = {Suying Lu and Junting Huang and Ruiqing Cai and Yan Gao and Jia Zhu and Juan Wang and Yi Que and Zijun Zhen and Feifei Sun and Huiqiang Huang and Yizhuo Zhang},
journal = {MedComm},
year = {2026},
month = nov,
doi = {10.1002/mco2.71128},
url = {https://europepmc.org/article/MED/42996901},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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.
AU - Suying Lu
AU - Junting Huang
AU - Ruiqing Cai
AU - Yan Gao
AU - Jia Zhu
AU - Juan Wang
AU - Yi Que
AU - Zijun Zhen
AU - Feifei Sun
AU - Huiqiang Huang
AU - Yizhuo Zhang
PY - 2026
DA - 2026/11/05
JO - MedComm
DO - 10.1002/mco2.71128
UR - https://europepmc.org/article/MED/42996901
AB - 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 Tmax 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.
SN - 2688-2663
ER -