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Clinical Trial
. 2025 Aug:206:108664.
doi: 10.1016/j.lungcan.2025.108664. Epub 2025 Jul 14.

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

Astrid Paulus  1 , Marius Zemaitis  2 , Saulius Cicenas  3 , Zanete Zvirbule  4 , Annika Sanfridson  5 , Camilla Rydberg Millrud  6 , Susanne Magnusson  7 , Nedjad Losic  8 , Dominique Tersago  9 , Ignacio Garcia-Ribas  10 , Lars Thorsson  11 , Luis G Paz-Ares  12
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Free article
Clinical Trial

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

Astrid Paulus et al. Lung Cancer. 2025 Aug.
Free article

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.

Keywords: Carcinoma; Nadunolimab; Non-small-cell lung; Pembrolizumab; Safety; Survival; Treatment efficacy.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Annika Sanfridson, Camilla Rydberg Millrud, Lars Thorsson, Susanne Magnusson, and Nedjad Losic are employees of Cantargia AB and own stock and/or stock options in Cantargia AB. Zanete Zvirbule reports payment from AstraZeneca for presentations, and support for attending meetings from F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme and AstraZeneca. Dominique Tersago reports consulting fees and reimbursement of travel costs from Cantargia AB. Ignacio Garcia-Ribas reports having been an employee of Cantargia AB and owns stock and/or stock options in Cantargia AB. He reports consulting fees from Cantargia AB and Oncomatryx, has been an external advisor for Oncomatryx. Luis G Paz-Ares reports grants from MSD, AstraZeneca, Pfizer and BMS, consulting fees from Lilly, MSD, Roche, Pharmamar, Merck, Astrazeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, and Daichii Sankyo, payment for presentations from AstraZeneca, Janssen, Merck, and Mirati. Astrid Paulus, Marius Zemaitis and Saulius Cicenas declare no conflicts of interest. .

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