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

Yuankai Shi; Xingsheng Hu; Xingya Li; Caifeng Gong; Ke Wang; Yongsheng Li; Shucai Zhang; Yongzhong Luo; Pingli Wang; Liyan Jiang; Xiangjiao Meng; Xiaorong Dong; Huijuan Wang; Runxiang Yang; Qi Mei; Baogang Liu; Limin Yang; Yinghui Sun

doi:10.1016/j.jtho.2024.01.015

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

J Thorac Oncol. 2024 Jan 29:S1556-0864(24)00035-2. doi: 10.1016/j.jtho.2024.01.015. Online ahead of print.

Authors

Yuankai Shi¹, Xingsheng Hu², Xingya Li³, Caifeng Gong², Ke Wang⁴, Yongsheng Li⁵, Shucai Zhang⁶, Yongzhong Luo⁷, Pingli Wang⁸, Liyan Jiang⁹, Xiangjiao Meng¹⁰, Xiaorong Dong¹¹, Huijuan Wang¹², Runxiang Yang¹³, Qi Mei¹⁴, Baogang Liu¹⁵, Limin Yang¹⁶, Yinghui Sun¹⁶

Affiliations

¹ 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. Electronic address: syuankai@cicams.ac.cn.
² 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.
³ Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, the People's Republic of China.
⁴ Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, the People's Republic of China.
⁵ Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, the People's Republic of China.
⁶ Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, the People's Republic of China.
⁷ 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.
⁸ Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, the People's Republic of China.
⁹ Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, the People's Republic of China.
¹⁰ Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, the People's Republic of China.
¹¹ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, the People's Republic of China.
¹² Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, the People's Republic of China.
¹³ Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan, the People's Republic of China.
¹⁴ 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.
¹⁵ Department of Respiratory Medicine, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, the People's Republic of China.
¹⁶ Shouyao Holdings (Beijing) Co.,Ltd., Beijing, the People's Republic of China.

PMID: 38295954
DOI: 10.1016/j.jtho.2024.01.015

Abstract

Introduction: Treatment options for second-generation (2^nd-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^rd-gen) ALK TKI, in patients with advanced ALK-positive non-small cell lung cancer.

Methods: This first-in-human, phase 1/2 study (Chinese Clinical Trial Registry identifier: ChiCTR1900025619; ClinicalTrials.gov 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.

Results: Between April 21, 2020, and August 31, 2023, a total of 127 patients with advanced ALK-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^nd-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.

Conclusions: Ficonalkib (SY-3505) was well tolerated, with favorable safety profiles and promising efficacy in patients resistant to prior 2^nd-gen ALK TKI.

Keywords: Anaplastic lymphoma kinase; Ficonalkib; Non–small cell lung cancer; Phase 1/2 study; Tyrosine kinase inhibitor.

Associated data

ClinicalTrials.gov/NCT05257512