• Traitements

  • Traitements systémiques : applications cliniques

  • Poumon

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

Mené sur 43 patients atteints d'un cancer du poumon non à petites cellules de stade avancé (âge médian : 64 ans), cet essai évalue l'efficacité, du point de vue du taux de réponse, de la survie sans progression et de la survie globale, et la toxicité d'un traitement de première ou deuxième ligne à base de nadunolimab (un anticorps anti-IL1RAP) en combinaison avec un doublet de chimiothérapie

Introduction: Interleukin-1 receptor accessory protein (IL1RAP), expressed in several tumors, is essential for IL-1

α 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.

Lung Cancer , résumé, 2025

Voir le bulletin