TY - JOUR
T1 - Deulorlatinib (TGRX-326) in ALK Gene Fusion Positive NSCLC After Failure of Second-Generation Inhibitors
T2 - A Single-Arm, Multicenter, Phase 2 Trial
AU - Huang, Jie
AU - Chen, Gang
AU - Wang, Zhehai
AU - Jin, Wenjian
AU - Zhao, Yanqiu
AU - Zhang, Yongchang
AU - Zhuang, Wu
AU - Xin, Ying
AU - Wang, Yan
AU - Zhou, Jianying
AU - Sun, Longhua
AU - Jin, Bo
AU - Zhang, Guifang
AU - Yao, Wenxiu
AU - Yi, Tienan
AU - Du, Xiaobo
AU - Ning, Fangling
AU - Chang, Jianhua
AU - Guo, Yubiao
AU - Hu, Ying
AU - Wang, Changli
AU - Ouyang, Weiwei
AU - Cai, Zhiqiang
AU - Han, Baohui
AU - Meng, Rui
AU - Ding, Zhenyu
AU - Su, Haichuan
AU - Li, Xingya
AU - Yu, Xinmin
AU - Chen, Mingwei
AU - Li, Gaofeng
AU - Zhang, Yan
AU - Wang, Jing
AU - Ma, Rui
AU - Gong, Beilei
AU - Cao, Chao
AU - Wu, Bo
AU - Lei, Chao
AU - Cao, Jingrong
AU - Zhao, Yuanyuan
AU - Zhou, Ting
AU - Zhao, Shen
AU - Huang, Yan
AU - Zhang, Li
AU - Yang, Yunpeng
N1 - Publisher Copyright:
© 2026 The Authors. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026
Y1 - 2026
N2 - Introduction: Deulorlatinib (TGRX-326), a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor, has reported promising activity and a favorable safety profile in ALK-positive NSCLC in a phase 1 trial. Here, we report the primary results of the pivotal phase 2 trial (NCT05955391) evaluating deulorlatinib in patients with ALK-positive NSCLC in whom second-generation ALK inhibitors had failed. Methods: This single-arm, phase 2 trial was conducted at 36 centers in China. Eligible patients received deulorlatinib 60 mg once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee (IRC). Key secondary end points included disease control rate, progression-free survival (PFS), duration of response, overall survival, intracranial efficacy, and safety. Exploratory biomarker analyses were performed using cell-free DNA. Results: The efficacy and safety analysis sets comprised 158 and 163 patients, respectively. The primary end point was met with an IRC-assessed ORR of 43.7% (95% confidence interval [CI], 35.8–51.8). The IRC-assessed median PFS was 11.1 months (95% CI, 8.3–13.7). Among patients with measurable central nervous system (CNS) metastases (n = 43), the intracranial ORR was 55.8% (95% CI, 39.9–70.9). In patients harboring the G1202R mutation (n = 8), robust activity was observed (ORR: 62.5%; disease control rate: 100%; median PFS: 11.0 months). The investigator-assessed results were consistent with the IRC-assessed findings. Treatment-related adverse events occurred in 96.3% of patients (47.2% grade ≥3). Nevertheless, dose modifications were infrequent (interruption, 13.5%; reduction, 11.0%; permanent discontinuation, 0.6%). The incidence of CNS-related treatment-related adverse events was 12.9%, with no patients interrupting or discontinuing treatment owing to CNS toxicity. Conclusions: Deulorlatinib indicated encouraging antitumor activity in patients with advanced ALK-positive NSCLC after failure of second-generation ALK inhibitors, including those with the G1202R mutation. Given its favorable safety profile, deulorlatinib represents a promising new option for this population.
AB - Introduction: Deulorlatinib (TGRX-326), a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor, has reported promising activity and a favorable safety profile in ALK-positive NSCLC in a phase 1 trial. Here, we report the primary results of the pivotal phase 2 trial (NCT05955391) evaluating deulorlatinib in patients with ALK-positive NSCLC in whom second-generation ALK inhibitors had failed. Methods: This single-arm, phase 2 trial was conducted at 36 centers in China. Eligible patients received deulorlatinib 60 mg once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee (IRC). Key secondary end points included disease control rate, progression-free survival (PFS), duration of response, overall survival, intracranial efficacy, and safety. Exploratory biomarker analyses were performed using cell-free DNA. Results: The efficacy and safety analysis sets comprised 158 and 163 patients, respectively. The primary end point was met with an IRC-assessed ORR of 43.7% (95% confidence interval [CI], 35.8–51.8). The IRC-assessed median PFS was 11.1 months (95% CI, 8.3–13.7). Among patients with measurable central nervous system (CNS) metastases (n = 43), the intracranial ORR was 55.8% (95% CI, 39.9–70.9). In patients harboring the G1202R mutation (n = 8), robust activity was observed (ORR: 62.5%; disease control rate: 100%; median PFS: 11.0 months). The investigator-assessed results were consistent with the IRC-assessed findings. Treatment-related adverse events occurred in 96.3% of patients (47.2% grade ≥3). Nevertheless, dose modifications were infrequent (interruption, 13.5%; reduction, 11.0%; permanent discontinuation, 0.6%). The incidence of CNS-related treatment-related adverse events was 12.9%, with no patients interrupting or discontinuing treatment owing to CNS toxicity. Conclusions: Deulorlatinib indicated encouraging antitumor activity in patients with advanced ALK-positive NSCLC after failure of second-generation ALK inhibitors, including those with the G1202R mutation. Given its favorable safety profile, deulorlatinib represents a promising new option for this population.
KW - ALK-positive NSCLC
KW - Deulorlatinib
KW - G1202R mutation
KW - Intracranial efficacy
KW - Tyrosine kinase inhibitors
UR - https://www.scopus.com/pages/publications/105039652783
U2 - 10.1016/j.jtho.2026.103737
DO - 10.1016/j.jtho.2026.103737
M3 - 文章
C2 - 42031067
AN - SCOPUS:105039652783
SN - 1556-0864
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
M1 - 103737
ER -