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

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2025-07-14 DOI:10.1016/j.lungcan.2025.108664

Astrid Paulus , Marius Zemaitis , Saulius Cicenas , Zanete Zvirbule , Annika Sanfridson , Camilla Rydberg Millrud , Susanne Magnusson , Nedjad Losic , Dominique Tersago , Ignacio Garcia-Ribas , Lars Thorsson , Luis G. Paz-Ares

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引用次数: 0

Abstract

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.

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抗il1rap抗体nadunolimab （CAN04）联合铂双药治疗晚期非小细胞肺癌患者的安全性、有效性和生物标志物分析

白细胞介素-1受体辅助蛋白（interleukin -1 receptor accessory protein, IL1RAP）在多种肿瘤中表达，是IL-1α和IL-1β信号转导导致肿瘤进展和治疗耐药的关键。Nadunolimab是一种完全人源化抗体依赖的细胞毒性增强单克隆抗体，靶向IL1RAP并阻断IL-1α/IL-1β信号传导。在非小细胞肺癌（NSCLC）（NCT03267316）患者中评估了纳都莫单抗联合铂基双重化疗的疗效和安全性。方法晚期NSCLC患者在派姆单抗后一线或二线接受纳都单抗+铂基双重化疗。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中肿瘤活检的免疫组织化学。结果纳入43例患者，中位年龄64岁，38%为女性，43%为派姆单抗后二线治疗。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例非鳞状组织患者中观察到最大的益处：中位生存期26.7个月，ORR 91%，包括两个完全缓解者（具有不同的生物标志物谱），1年生存率82%。生物标志物分析显示，与治疗naïve患者相比，二线pembrolizumab后患者的肿瘤浸润免疫细胞水平提高。3+级中性粒细胞减少症、贫血和血小板减少症的发生率高于先前单独铂基双重化疗的报道。结论奈都利单抗联合铂基双药化疗治疗晚期NSCLC疗效良好，非鳞状组织患者在派姆单抗复发后二线治疗获益最大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.