Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, PR China.
Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, PR China.
Clin Lung Cancer. 2024 Dec;25(8):e393-e396. doi: 10.1016/j.cllc.2024.07.006. Epub 2024 Aug 1.
Cadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration.
This single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response.
The study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025.
Cadonilimab 是一种首创的 PD-1/CTLA-4 双特异性抗体。丝氨酸/苏氨酸激酶（STK11）突变与非小细胞肺癌（NSCLC）中低 PD-L1 表达和客观缓解率（ORR）相关，导致无进展生存期（PFS）和总生存期（OS）较差。在此，我们假设 Cadonilimab 联合化疗可以增强这些患者的抗肿瘤免疫并延长生存期。因此，我们设计了这项研究，以探索 Cadonilimab 联合化疗在携带 STK11 改变的晚期/转移性 NSCLC 患者中的临床活性和安全性。
这是一项在广州医科大学第一附属医院进行的单中心、开放标签、单臂 II 期试验。本研究纳入携带 STK11 突变的治疗初治的晚期/转移性 NSCLC 患者。符合条件的患者将接受 Cadonilimab（第 1 天 10mg/kg）联合培美曲塞（500mg/m）和卡铂（AUC=5）治疗非鳞状 NSCLC，或联合紫杉醇（100mg/m）和卡铂（AUC=5）治疗鳞状 NSCLC，共 4 个周期，随后进行维持治疗（Cadonilimab 联合培美曲塞或紫杉醇）。当疾病进展、Cadonilimab 不耐受和/或化疗不耐受时，停止治疗。根据实体瘤反应评价标准（1.1）评估可测量病变。主要终点是 ORR 和安全性。次要终点包括 PFS、疾病控制率和缓解持续时间。
该研究于 2023 年 9 月开始入组，预计于 2025 年 1 月得出主要终点的初步结果。
