Alirocumab plus cemiplimab in advanced immuno-refractory metastatic non-small cell lung cancer: an ongoing multi-center phase II study
Year: 2026
Type: article
Study design: Study Protocol
Abstract: 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. Why is this study needed? Scientists found that a protein called PCSK9 does more than help control cholesterol. It may also help cancer cells hide from the body’s immune system. In lab tests, when PCSK9 is blocked, cancer cells keep more “ID tags” on their surface. These tags help the immune system see the cancer and attack it. Medicines that block PCSK9, like alirocumab, are already approved and used to lower cholesterol. Because these medicines are safe and well known, doctors want to see if adding a PCSK9 blocker to immunotherapy can help people whose cancer no longer responds to treatment. TOP2201 is a phase II study. It is testing whether using alirocumab with cemiplimab can help people with advanced lung cancer (NSCLC) after their cancer has grown on earlier immunotherapy. The study is for adults with stage IV NSCLC. Potential impact: If this treatment works, TOP2201 may show that adding a PCSK9 blocker can help the immune system fight lung cancer again in people who have very few options left.
Source: Figshare
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7150783756