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

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 1, 2027

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Alirocumab and Cemiplimab
    • Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab

Clinical Trial Outcome Measures

Primary Measures

  • Response rate associated with combination of alirocumab and cemiplimab
    • Time Frame: 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
    • 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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Duke University
  • Collaborator
    • Regeneron Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Scott Antonia, MD, 919 681 9509, scott.antonia@duke.edu

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