PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung

A Phase II Study of PCSK9 Inhibitor Alirocumab and PD-1 Inhibitor Cemiplimab in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung Cancer: TOP2201

PCSK9 mediates immune checkpoint blockade resistance by downregulating tumor cell surface MHC class 1 molecules. This study will evaluate if combining the anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab can generate anti-tumor activity and clinical responses in patients with metastatic lung cancer who have progressed on first line immune checkpoint blockade therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Combination product: Alirocumab and Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically documented recurrent and/or metastatic non-small cell lung cancer
• Progression after prior PD-1 directed therapy (as monotherapy or in combination with chemotherapy and/or anti-CTLA4, or anti-VEGF agents) - defined as investigator assessed progression from prior treatment
• If molecularly altered NSCLC including EGFR, ALK, ROS1, MET exon 14, RET, BRAF, NTRK, progression on prior targeted therapy is required
• Measurable disease by RECIST 1.1
• ECOG Performance Status 0 or 1
• Signed written informed consent
• Minimum of 4 weeks from any other experimental anti-cancer therapies or prior PD-1 treatment
• Meet all the laboratory criteria per protocol

Exclusion Criteria:

• Prior treatment with PCSK9 inhibitors
• Cardiac issues including MI, uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications.
• Uncontrolled diabetes mellitus, defined as HbA1c > 10
• Major surgery less than 4 weeks prior to study enrollment
• Another malignant condition diagnosed within 3 years of study enrollment
• Intolerance to prior PD-1/L1 treatment including discontinuation for severe or recurrent severe toxicity (including myocarditis or other myocardiotoxity, encephalitis, colitis, diarrhea, pancreatitis, hypo/hyperthyroidism, hypopituitarism, adrenal insufficiency, rash, autonomic neuropathy, myasthenia gravis, Guillain-Barre, myositis/polymyositis, hepatitis, Type 1 Diabetes, thrombocytopenia) or developed an immune checkpoint blockade related immune adverse event that was refractory to steroids and required additional systemic immunosuppressive medication.
• Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS)
• Additional exclusion criterion as per listed in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alirocumab and Cemiplimab; Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab	Combination product: Alirocumab and Cemiplimab; Combination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate associated with combination of alirocumab and cemiplimab	Ascertain the response rate associated with alirocumab and cemiplimab, with 95% confidence intervals. Response rate is defined as the proportion of treated subjects with a complete or partial response per RECIST 1.1 criteria. All patients who receive at least one dose of alirocumab and cemiplimab will be considered for the primary outcome analysis	Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks per RECIST 1.1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of the combination regimen	Toxicity analysis will be performed on a continual basis following CTC V 5.0 criteria	Day 1 of treatment until 30 days post last dose
Progression Free Survival	Progression Free Survival will be assessed utilizing RECIST 1.1 criteria	Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks
Overall survival	Patients will be followed till death or off study due to any other reason	Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Oduah EI, Zhang T, Jung SH, Stinchcombe TE, Ready N, Crawford J, Clarke JM, Gray JE, Antonia SJ. Alirocumab plus cemiplimab in advanced immuno-refractory metastatic non-small cell lung cancer: an ongoing multi-center phase II study. Future Oncol. 2026 Apr 6:1-8. doi: 10.1080/14796694.2026.2648863. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2023
• Primary Completion (Actual): September 16, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; PCSK9 Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antimetabolites; Serine Proteinase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; cemiplimab; alirocumab
• Other Study ID Numbers: PRO00111111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No