本研究旨在评估卡多尼利替单抗（抗PD-1和CTLA-4双特异性抗体）在先前治疗过的转移性非小细胞肺癌（NSCLC）患者中的疗效和安全性。在这项多中心、开放标签的Ib/II期研究中，纳入了先前治疗过NSCLC的患者，分为三个不同的队列：A队列，先前铂类双联化疗失败并未接受免疫疗法的患者；B队列，先前铂类双联化疗失败且对免疫疗法（IO）有原发性抵抗性的患者；C队列，先前铂类双联化疗失败且对IO有获得性抵抗的患者。符合条件的患者每两周静脉注射卡多尼利替单抗6mg/kg。主要终点是根据实体瘤反应评价标准1.1版的客观缓解率（ORR）。总共纳入了53名患者：A队列30名患者，B队列7名患者，C队列16名患者。A队列的ORR为10%，B队列和C队列均未出现缓解患者。A队列、B队列和C队列的中位无进展生存期分别为19.61个月（95% CI，11.30-NE），4.93个月（95% CI，1.97-NE）和13.16个月（95% CI，6.18-NE）。有6名患者（11.3%）报告了3-4级与治疗相关的不良事件，包括丙氨酸氨基转移酶增加（1.9%）、皮疹（1.9%）、胸闷（1.9%）、高钙血症（1.9%）、贫血（1.9%）和输液相关反应（1.9%）。本研究未达到主要终点。卡多尼利替单抗在免疫疗法失败的患者中显示出有限的疗效，尤其是原发性抵抗的情况。然而，在先前铂类双联化疗失败且未经免疫疗法的患者中，卡多尼利替单抗可能作为二线免疫单药治疗的一个选择，因为其疗效与其他首线化疗后的免疫检查点抑制剂类似。卡多尼利替单抗具有良好的耐受性和轻微的毒性，使其成为联合策略的潜在候选药物。临床试验号NCT04172454。版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。

This study aimed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in patients with previously treated metastatic non-small-cell lung cancer (NSCLC).In this multicenter, open-label, phase Ib/II study, patients with previously treated NSCLC were enrolled in three different cohorts: Cohort A, patients who had failed previous platinum-based doublet chemotherapy and were immunotherapy naïve; Cohort B, patients who had failed previous platinum-based doublet chemotherapy and had primary resistance to immunotherapy (IO); Cohort C, patients who had failed previous platinum-based doublet chemotherapy and had acquired resistance to IO. Eligible patients were given cadonilimab 6 mg/kg intravenously every 2 weeks. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1.A total of 53 patients were enrolled: including 30 patients in cohort A, 7 in cohort B, and 16 in cohort C. ORR was 10% in cohort A, and there were no responder in cohort B and cohort C. Median overall survival was 19.61 (95% CI 11.30-NE) months, 4.93 (95% CI 1.97-NE) months and 13.16 (95% CI 6.18-NE) months in cohort A, B and C, respectively. Grade 3-4 treatment-related adverse events were reported in 6 (11.3 %) patients, including alanine aminotransferase increased (1.9%), rash (1.9%), chest discomfort (1.9%), hypercalcaemia (1.9%), anaemia (1.9%) and infusion related reaction (1.9%).The study did not meet its primary endpoint. Cadonilimab demonstrated limited efficacy in patients with IO failure, especially in cases of primary resistance. However, cadonilimab might play a role as a second-line immune monotherapy after platinum-based doublet chemotherapy failure and IO naïve, as its efficacy is similar to other immune checkpoint inhibitors after first-line chemotherapy. Cadonilimab was well-tolerated with mild toxicity, making it a potential candidate for the combination strategy. Clinical trial number NCT04172454.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.