Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
Deulorlatinib (TGRX-326) in ALK Gene Fusion Positive NSCLC After Failure of Second-Generation Inhibitors: A Single-Arm, Multicenter, Phase 2 Trial.
СтатьяМногоцентровое исследованиеКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Huang Jie, Chen Gang, Wang Zhehai, Jin Wenjian, Zhao Yanqiu, Zhang Yongchang, Zhuang Wu, Xin Ying, Wang Yan, Zhou Jianying, Sun Longhua, Jin Bo, Zhang Guifang, Yao Wenxiu, Yi Tienan, Du Xiaobo, Ning Fangling, Chang Jianhua, Guo Yubiao, Hu Ying, Wang Changli, Ouyang Weiwei, Cai Zhiqiang, Han Baohui, Meng Rui, Ding Zhenyu, Su Haichuan, Li Xingya, Yu Xinmin, Chen Mingwei, Li Gaofeng, Zhang Yan, Wang Jing, Ma Rui, Gong Beilei, Cao Chao, Wu Bo, Lei Chao, Cao Jingrong, Zhao Yuanyuan, Zhou Ting, Zhao Shen, Huang Yan, Zhang Li, Yang Yunpeng
Аннотация
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.
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.