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

Duke University

Status and phase

Enrolling

Phase 2

Conditions

Non-small Cell Lung Cancer (NSCLC)

Treatments

Combination Product: Alirocumab and Cemiplimab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05553834

PRO00111111

Details and patient eligibility

About

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.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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