A Patient-Centric, Open-Label, Multicenter, Phase II Study of Lorlatinib Monotherapy in the First-Line Treatment of Patients With locally Advanced or Metastatic ALK-Positive Non-Small Cell Lung Cancer (CTONG2203)

Jia-Xin Lin; Qing Zhou; Hong-Hong Yan; An-Wen Liu; Guo-Wu Wu; Qian Chu; Ying-Ying Du; Jiu-Wei Cui; Ying Cheng; Yi Yang; Hai-Peng Xu; Hai-Yan Tu; Yi-Long Wu; Si-Yang Maggie Liu

doi:10.1016/j.cllc.2025.05.014

A Patient-Centric, Open-Label, Multicenter, Phase II Study of Lorlatinib Monotherapy in the First-Line Treatment of Patients With locally Advanced or Metastatic ALK-Positive Non-Small Cell Lung Cancer (CTONG2203)

Clin Lung Cancer. 2025 May 28:S1525-7304(25)00127-5. doi: 10.1016/j.cllc.2025.05.014. Online ahead of print.

Authors

Jia-Xin Lin¹, Qing Zhou¹, Hong-Hong Yan¹, An-Wen Liu², Guo-Wu Wu³, Qian Chu⁴, Ying-Ying Du⁵, Jiu-Wei Cui⁶, Ying Cheng⁷, Yi Yang⁸, Hai-Peng Xu⁹, Hai-Yan Tu¹, Yi-Long Wu¹⁰, Si-Yang Maggie Liu¹¹

Affiliations

¹ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
² Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
³ Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China.
⁴ Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
⁶ Cancer Center, The First Hospital of Jilin University, Changchun, China.
⁷ Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China.
⁸ Department of Thoracic Surgery, The Third People's Hospital of Chengdu, Chengdu, China.
⁹ Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou, China.
¹⁰ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. Electronic address: syylwu@live.cn.
¹¹ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Department of Medical Affairs, Chinese Thoracic Oncology Group (CTONG), Guangzhou, China. Electronic address: siyangliu2020@outlook.com.

PMID: 40541556
DOI: 10.1016/j.cllc.2025.05.014

Abstract

Background: Lorlatinib is a potent third-generation ALK tyrosine kinase inhibitor (TKI). CROWN study demonstrated remarkable efficacy and manageable toxicity of first-line lorlatinib treatment for advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. However, only 10 ALK-positive NSCLC patients were randomized to the lorlatinib group in China mainland. There is a vast vacancy of efficacy and safety regarding first-line lorlatinib treatment in China advanced ALK-positive NSCLC. Additionally, understanding of the benefit-risk profile of lorlatinib in a broader population and real-world data of diversity of ALK-TKIs are limited.

Patients and methods: We adopted a patient-centric trial (PCT) design to provide more generalizable data to better inform clinical decision-making. This is a 3 cohorts, open-label, multicenter, phase II study (CTONG2203), conducted to prospectively enroll 189 treatment-naïve patients with advanced ALK-positive NSCLC in China, which was divided into 2 treatment intervention cohorts and real-world observing (RO) cohort. The treatment intervention cohorts include restrictive eligibility criteria "CROWN criteria (CC) cohort," and broadening eligibility criteria "Expand Eligibility Criteria (EC) cohort," who will receive first-line lorlatinib treatment. And we concomitantly set up a prospective RO cohort to observe the clinical outcomes of these patients treated with different ALK-TKI who received physician's therapy of choice.

Conclusion: This patient-centric study will contribute data on efficacy, safety and resistance mechanism of first-line lorlatinib, and offer better perspectives on the current status of real-world treatment of ALK-TKIs in advanced ALK-positive NSCLC in China.

Clinical trial registration: NCT06092086 (CTONG 2203).

Keywords: Patient-centric trial; Phase II study , “CROWN criteria (CC) cohort”, “Expand Eligibility Criteria (EC) cohort”, Real-world observing (RO) cohort..

Associated data

ClinicalTrials.gov/NCT06092086