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

Sponsor: Duke University

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT05553834

Patient View

This study assesses the combination of alirocumab and cemiplimab in patients with metastatic NSCLC who progressed after prior PD-1 therapy. Eligible participants must have measurable disease, ECOG 0-1, and meet lab criteria. Exclusions include prior PCSK9 inhibitor use and certain health conditions. The intervention involves alirocumab 150mg SC biweekly and cemiplimab 350mg IV triweekly.

Patient Parameters

Program Overview

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.

Eligibility Criteria

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

Get This Program In Your Inbox

You can sign up and apply your patients for this program.