Ficonalkib (SY-3505) in Advanced ALK-Positive NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 1/2 Study,Journal of Thoracic Oncology

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Ficonalkib (SY-3505) in Advanced ALK-Positive NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 1/2 Study
Journal of Thoracic Oncology ( IF 21.0 ) Pub Date : 2024-01-29 , DOI: 10.1016/j.jtho.2024.01.015
Yuankai Shi ₁ , Xingsheng Hu ₁ , Xingya Li ₂ , Caifeng Gong ₁ , Ke Wang ₃ , Yongsheng Li ₄ , Shucai Zhang ₅ , Yongzhong Luo ₆ , Pingli Wang ₇ , Liyan Jiang ₈ , Xiangjiao Meng ₉ , Xiaorong Dong ₁₀ , Huijuan Wang ₁₁ , Runxiang Yang ₁₂ , Qi Mei ₁₃ , Baogang Liu ₁₄ , Limin Yang ₁₅ , Yinghui Sun ₁₅

Affiliation

Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, the People's Republic of China.
Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, the People's Republic of China.
Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, the People's Republic of China.
Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, the People's Republic of China.
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, the People's Republic of China.
Thoracic Medicine Department 1, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, the People's Republic of China.
Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, the People's Republic of China.
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, the People's Republic of China.
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, the People's Republic of China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, the People's Republic of China.
Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, the People's Republic of China.
Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan, the People's Republic of China.
Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, the People's Republic of China.
Department of Respiratory Medicine, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, the People's Republic of China.
Shouyao Holdings (Beijing) Co.,Ltd., Beijing, the People's Republic of China.

Treatment options for second-generation (2-gen) ALK tyrosine kinase inhibitor (TKI)-resistant patients are limited. We evaluated the safety, pharmacokinetics, and efficacy of ficonalkib (SY-3505), a third-generation (3-gen) ALK TKI, in patients with advanced -positive non-small cell lung cancer. This first-in-human, phase 1/2 study (Chinese Clinical Trial Registry identifier: ChiCTR1900025619; identifier: NCT05257512) had two parts. Phase 1 included a dose-escalation phase (25–800 mg quaque die [QD]) and a dose-expansion phase (500 mg QD or 600 mg QD). Phase 2 enrolled patients treated at recommended phase 2 dose. Primary end points were safety in phase 1 and objective response rate (ORR) in phase 2. Between April 21, 2020, and August 31, 2023, a total of 127 patients with advanced -positive non-small cell lung cancer were enrolled, with 62 in phase 1. Ficonalkib was well absorbed and tolerated, with one dose-limited toxicity event occurring at 800 mg QD. Treatment-related adverse events occurred in 85.5% of patients, with 19.4% experienced greater than or equal to grade 3 events. The ORR was 38.3% (23 of 60, 95% confidence interval [CI]: 26.1%–51.8%) in phase 1, and 600 mg QD was established as recommended phase 2 dose. In phase 2, a total of 65 patients received ficonalkib at 600 mg QD. In total, 88 patients received ficonalkib at 600 mg QD in phase 1/2, and all had received prior 2-gen ALK TKI treatment. Furthermore, 90.9% of the patients experienced treatment-related adverse events and 14.8% experienced greater than or equal to grade 3 events. The ORR in efficacy-assessable patients who received ficonalkib at 600 mg QD was 47.5% (38 of 80, 95% CI: 36.2%–59.0%), with an intracranial ORR of 37.5% (12 of 32, 95% CI: 21.1%–56.3%) in these patients with measurable brain lesions at baseline. Ficonalkib (SY-3505) was well tolerated, with favorable safety profiles and promising efficacy in patients resistant to prior 2-gen ALK TKI.

更新日期：2024-01-29

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