This phase II trial tests the safety and effectiveness of alirocumab (a PCSK9 inhibitor) in combination with cemiplimab (a PD-1 inhibitor) in treating patients with stage IV non-small cell lung cancer that have progressed on prior anti-PD-1 therapy. Alirocumab injection is in a class of medications called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor monoclonal antibodies. PCSK9 inhibitors are a type of cholesterol-lowering medicine. It works by lowering your levels of low-density lipoprotein cholesterol (LDL-C), also known as “bad cholesterol.” Cemiplimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. PD-1 inhibitors and PD-L1 inhibitors are a group of anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Combing the anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab may help to generate anti-tumor activity and clinical responses in participants with metastatic lung cancer that have progressed on prior PD-1 inhibitors.
Additional locations may be listed on ClinicalTrials.gov for NCT05553834.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To study the clinical activity (response rate as assessed by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) of PCSK-9 inhibitor alirocumab in combination with cemiplimab in patients with locally advanced or metastatic non-small cell lung cancer who have progressed on prior therapy with an anti-PD1/L1 agent.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of the combination regimen.
II. To evaluate secondary efficacy endpoints of the combination regimen;
IIa. Disease control rate (stable disease [SD], partial response [PR], and complete response [CR]);
IIb. Complete response rates;
IIc. Progression free survival per RECIST 1.1 criteria;
IId. Overall survival;
IIe. Duration of responses.
EXPLORATORY OBJECTIVES:
I. To evaluate the pharmacodynamic marker of the change in low-density lipoprotein (LDL) cholesterol levels measured in serial plasma collections while on treatment with alirocumab.
OUTLINE:
Patients receive alirocumab subcutaneously (SC) every 2 weeks (Q2W) and cemiplimab intravenously (IV) every 3 weeks (Q3W) of each cycle. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) at baseline, computed tomography (CT) scans at baseline, every cycle, at restaging, and during follow-up, and collection of blood samples at screening, on day 1 of cycles 1 and 2, at disease progression or discontinuation of study treatment, and during follow-up.
After completion of the study treatment, patients are followed up at 28 days and every 3 months for up to 5 years after the last patient is enrolled or until the study is closed (whichever comes first).
Lead OrganizationDuke University Medical Center
Principal InvestigatorScott J. Antonia
