抗IL1RAP抗体纳杜诺单抗（CAN04）联合铂类双联方案治疗晚期非小细胞肺癌患者的安全性、疗效及生物标志物分析
Safety, efficacy, and analysis of biomarkers in patients with advanced non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab (CAN04) in combination with platinum doublet.
作者信息
Paulus Astrid, Zemaitis Marius, Cicenas Saulius, Zvirbule Zanete, Sanfridson Annika, Millrud Camilla Rydberg, Magnusson Susanne, Losic Nedjad, Tersago Dominique, Garcia-Ribas Ignacio, Thorsson Lars, Paz-Ares Luis G
机构信息
Centre Hospitalier Universitaire de Liège, Avenue de l'Hôpital 1, 4000 Liège, Belgium.
Department of Pulmonology Medical Academy, Lithuania University of Health Science A. Mickevičiaus g. 9, LT-44307 Kaunas, Lithuania.
出版信息
Lung Cancer. 2025 Aug;206:108664. doi: 10.1016/j.lungcan.2025.108664. Epub 2025 Jul 14.
INTRODUCTION
Interleukin-1 receptor accessory protein (IL1RAP), expressed in several tumors, is essential for IL-1α and IL-1β signaling which leads to tumor progression and treatment resistance. Nadunolimab, a fully humanized antibody-dependent cellular cytotoxicity-enhanced monoclonal antibody, targets IL1RAP and blocks IL-1α/IL-1β signaling. Efficacy and safety of nadunolimab plus platinum-based doublet chemotherapies were assessed in patients with non-small cell lung cancer (NSCLC) (NCT03267316).
METHODS
Patients with advanced NSCLC received nadunolimab plus platinum-based doublet chemotherapies in first-line or second-line post-pembrolizumab. Study objectives included the anti-tumor response, progression-free survival (PFS), overall survival (OS), levels of biomarkers in serum, and immunohistochemistry of baseline and on-treatment tumor biopsies.
RESULTS
43 patients were enrolled, median age 64 years, 38 % female, and 43 % were treated in second-line post-pembrolizumab. Median PFS was 7.2 months (95 % CI 5.6-9.2), median OS was 13.7 months (95 % CI 11.1-18.3), and 1-year survival was 54 %. The greatest benefits were observed in 11 patients with non-squamous histology treated in second-line post-pembrolizumab: median OS 26.7 months, ORR 91 % including two complete responders (with distinct biomarker profiles), and 1-year survival 82 %. Biomarker analyses showed that patients in second-line post-pembrolizumab had an enhanced level of tumor-infiltrating immune cells compared to treatment naïve patients. Rates of Grade 3+ neutropenia, anemia, and thrombocytopenia were higher than previous reports of platinum-based doublet chemotherapies alone.
CONCLUSIONS
Nadunolimab plus platinum-based doublet chemotherapies showed promising efficacy in advanced NSCLC, with the greatest benefit in patients with non-squamous histology treated in second line after relapsing on pembrolizumab treatment.
简介
白细胞介素-1受体辅助蛋白（IL1RAP）在多种肿瘤中表达，对于导致肿瘤进展和治疗耐药的IL-1α和IL-1β信号传导至关重要。纳杜诺利单抗是一种完全人源化的抗体依赖性细胞毒性增强型单克隆抗体，靶向IL1RAP并阻断IL-1α/IL-1β信号传导。在非小细胞肺癌（NSCLC）患者中评估了纳杜诺利单抗联合铂类双药化疗的疗效和安全性（NCT03267316）。
方法
晚期NSCLC患者在一线或帕博利珠单抗治疗后的二线接受纳杜诺利单抗联合铂类双药化疗。研究目标包括抗肿瘤反应、无进展生存期（PFS）、总生存期（OS）、血清生物标志物水平以及基线和治疗期间肿瘤活检的免疫组织化学。
结果
共纳入43例患者，中位年龄64岁，38%为女性，43%在帕博利珠单抗治疗后的二线接受治疗。中位PFS为7.2个月（95%CI 5.6 - 9.2），中位OS为13.7个月（95%CI 11.1 - 18.3），1年生存率为54%。在11例帕博利珠单抗治疗后的二线接受治疗的非鳞状组织学患者中观察到最大获益：中位OS为26.7个月，客观缓解率（ORR）为91%，包括两名完全缓解者（具有不同的生物标志物谱），1年生存率为82%。生物标志物分析表明，与未接受过治疗的患者相比，帕博利珠单抗治疗后的二线患者肿瘤浸润免疫细胞水平有所提高。3级及以上中性粒细胞减少、贫血和血小板减少的发生率高于既往单独铂类双药化疗的报道。
结论
纳杜诺利单抗联合铂类双药化疗在晚期NSCLC中显示出有前景的疗效，对帕博利珠单抗治疗后复发的二线非鳞状组织学患者获益最大。
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