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

NCT05553834 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00111111
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Safety and tolerability of the combination regimen

  Day 1 of treatment until 30 days post last dose

• Progression Free Survival

  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

  Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks

Study Arms (1)

Alirocumab and Cemiplimab

EXPERIMENTAL

Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab

Combination Product: Alirocumab and Cemiplimab

Interventions

Alirocumab and Cemiplimab COMBINATION_PRODUCT

Combination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks

Alirocumab and Cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Duke University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Related Publications (1)

• 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.

  PMID: 41940540 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alirocumab; cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 23, 2022
• Study Start: May 16, 2023
• Primary Completion: September 16, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)