Safety, tolerability, and preliminary efficacy of nadunolimab, an anti-IL- 1 receptor accessory protein monoclonal antibody, in combination with pembrolizumab in patients with solid tumors

• DOI: 10.1007/s10637-025-01538-3
• Publication Date: 2025-05-01T07:02:37Z
• Authors: Roger B. Cohen; Antonio Jimeno; Jennifer Hreno; Lova Sun; Marie Wallén-Öhman; Camilla Rydberg M...; Annika Sanfridson; Ignacio Garcia-Ribas
• Keywords: Tolerability

Interleukin (IL)-1 signaling has an essential role in tumor progression and immunosuppression is linked to acquired resistance anti-PD-1/PD-L1 treatment. Nadunolimab IL1RAP (IL-1 receptor accessory protein)-targeting antibody that blocks IL-1α/IL-1β enhanced antibody-dependent cellular cytotoxicity. We investigated the safety preliminary efficacy of nadunolimab with pembrolizumab patients metastatic solid tumors who had progressed on previous checkpoint inhibitor treatment, suggesting (NCT04452214). This phase 1b trial enrolled disease exhausted or declined standard-of-care alternatives. Patients received (5 mg/kg) standard-dose pembrolizumab. The primary objective was assess safety. Secondary objectives were anti-tumor response as per iRECIST, pharmacokinetics, changes immune mediators. Fifteen stage IV cancer (head neck squamous cell carcinoma, non-small lung cancer, melanoma) entered trial. Grade ≥ 3 adverse events reported for 7 (47%). There one dose-limiting toxicity febrile neutropenia. most frequent grade event dysphagia (two patients). Seven (47%) reductions target lesion size. Median iPFS 3.4 months (95% CI 1.4-8.6). OS 19.7 4.3-28.7) 67% 1-year survival. Survival significantly longer higher baseline infiltration CD163 + macrophages natural killer cells reduced on-treatment circulating IL-6 levels neutrophil-to-lymphocyte ratio. acceptable profile, prolonged control observed a subset patients. results support further development combination inhibitors.