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

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). 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. 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. 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.