This phase II trial compares the effect of adding alirocumab to chemotherapy plus cemiplimab versus chemotherapy plus cemiplimab alone prior to surgery for patients with stage IB-IIIA non-small cell lung cancer (NSCLC). Researchers want to know if combining alirocumab with cemiplimab can generate anti-tumor activity and clinical responses in these patients. Lung cancer in its earlier stages can sometimes be cured by surgery. However, there is still a significant chance that it will come back (relapse), and studies are being done to find ways to improve patients’ outcomes. One approach is to give anti-cancer drugs before surgery (called neoadjuvant therapy) to reduce the chances of a relapse. One of these drugs, known as alirocumab, is a PCSK9 inhibitor. PCSK9 inhibitors are a type of cholesterol-lowering drug. It works by lowering levels of low-density lipoprotein cholesterol (LDL-C), also known as “bad cholesterol” which may reduce cardiovascular events in patients with heart disease. Programmed cell death protein 1 (PD-1) inhibitors and programmed cell death 1 ligand (PD-L1) inhibitors, such as cemiplimab, are a group of anticancer drugs that block the activity of PD-1 and PD-L1 immune checkpoint proteins present on the surface of cells. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving alirocumab with chemotherapy and cemiplimab may be safe, tolerable and/or effective in treating patients with stage IB-IIIA NSCLC.
Additional locations may be listed on ClinicalTrials.gov for NCT06385262.
Locations matching your search criteria
United States
North Carolina
Durham
Duke University Medical CenterStatus: Active
Contact: Neal E. Ready
Phone: 919-684-7218
PRIMARY OBJECTIVE:
I. To compare pathologic complete response (pCR) rate for neoadjuvant chemotherapy plus cemiplimab versus chemotherapy, cemiplimab, and alirocumab.
SECONDARY OBJECTIVES:
I. To assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab:
a) Objective response rate;
b) Event-free survival;
c) Overall survival.
II. To determine the safety, and tolerability of neoadjuvant chemotherapy and cemiplimab with alirocumab in early-stage non-small cell lung cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate the difference in tumor infiltrating lymphocytes (TILs) and dendritic cells (through immunohistochemistry [IHC], fluorescence activated cell sorting [FACs] analysis, and bulk ribonucleic acid measurement [RNA]-sequencing [seq] with CIBERSORT) from surgical specimens from patients treated with neoadjuvant chemotherapy and cemiplimab with alirocumab versus surgical specimens from patients receiving neoadjuvant chemotherapy plus cemiplimab.
II. To explore potential associations between blood biomarker measures and anti-tumor activity.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive 1 of 4 chemotherapy regimens: a) Carboplatin intravenously (IV) or cisplatin IV and paclitaxel IV; b) Docetaxel IV and cisplatin IV or carboplatin IV; c) Gemcitabine IV and cisplatin IV or carboplatin IV; d) Pemetrexed IV and cisplatin IV or carboplatin IV. Patients also receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive alirocumab subcutaneously (SC) once every 4 weeks (Q4W) in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive 1 of 4 chemotherapy regimens as stated in Arm I. Patients also receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity.
All patients undergo surgery 3-12 weeks after completion of neoadjuvant treatment, followed by standard of care therapies as clinically indicated. Additionally, all patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) and/or positron emission tomography (PET)/CT during screening, tissue collection on study, and blood collection and CT throughout the study.
After completion of study treatment, patients are followed up for 30 days and then every 3-4 months up to 2 years.
Lead OrganizationDuke University Medical Center
Principal InvestigatorNeal E. Ready