Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer, Guangzhou, China.
Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
Lung Cancer. 2023 Oct;184:107355. doi: 10.1016/j.lungcan.2023.107355. Epub 2023 Aug 29.
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.
本研究旨在评估卡度尼利单抗（抗 PD-1 和 CTLA-4 双特异性抗体）在先前治疗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、Ib/II 期研究中，先前治疗的 NSCLC 患者被纳入三个不同的队列：队列 A，先前接受过铂类双联化疗且免疫治疗初治的患者；队列 B，先前接受过铂类双联化疗且对免疫治疗（IO）原发耐药的患者；队列 C，先前接受过铂类双联化疗且对 IO 获得性耐药的患者。符合条件的患者接受 6mg/kg 卡度尼利单抗静脉输注，每 2 周一次。主要终点是根据实体瘤反应评价标准 1.1 版（Response Evaluation Criteria in Solid Tumors version 1.1）评估的客观缓解率（ORR）。
共纳入 53 例患者：队列 A 30 例，队列 B 7 例，队列 C 16 例。队列 A 的 ORR 为 10%，队列 B 和队列 C 均无应答者。队列 A、B 和 C 的中位总生存期分别为 19.61（95%CI 11.30-NE）个月、4.93（95%CI 1.97-NE）个月和 13.16（95%CI 6.18-NE）个月。6（11.3%）例患者发生 3-4 级治疗相关不良事件，包括丙氨酸氨基转移酶升高（1.9%）、皮疹（1.9%）、胸部不适（1.9%）、高钙血症（1.9%）、贫血（1.9%）和输注相关反应（1.9%）。
该研究未达到主要终点。卡度尼利单抗在 IO 失败的患者中显示出有限的疗效，特别是在原发耐药的情况下。然而，卡度尼利单抗可能在铂类双联化疗失败和 IO 初治后作为二线免疫单药治疗发挥作用，因为其疗效与一线化疗后其他免疫检查点抑制剂相似。卡度尼利单抗具有良好的耐受性，毒性轻微，可能成为联合治疗策略的候选药物。临床试验编号 NCT04172454。
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