Alirocumab plus cemiplimab in advanced immuno-refractory metastatic non-small cell lung cancer: an ongoing multi-center phase II study.

Immunotherapy resistance represents a major unmet clinical need for patients with metastatic non-small cell lung cancer (NSCLC). Preclinical studies have identified PCSK9 as an immunosuppressive regulator of antigen presentation, providing a compelling rationale for therapeutic PCSK9 inhibition as a strategy to overcome resistance to immune checkpoint blockade. Building on this evidence, we present the scientific rationale and study design of TOP2201, an ongoing single-arm phase II trial evaluating the addition of the PCSK9 inhibitor alirocumab to anti-PD-1 therapy in patients with metastatic NSCLC who have experienced disease progression on prior immune checkpoint inhibitor-based regimens. The primary endpoint is objective response rate, with secondary endpoints assessing additional efficacy outcomes and safety. Findings from TOP2201 are expected to generate preliminary clinical and safety data on this combination strategy in the immunorefractory NSCLC setting.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT05553834.