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

Phase 2
Recruiting
Conditions
Non-small Cell Lung Cancer (NSCLC)
Interventions
Combination Product: Alirocumab and Cemiplimab
Registration Number
NCT05553834
Lead Sponsor
Duke University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Alirocumab and CemiplimabAlirocumab and CemiplimabCombination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab
Primary Outcome Measures
NameTimeMethod
Response rate associated with combination of alirocumab and cemiplimabDay 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 Outcome Measures
NameTimeMethod
Progression Free SurvivalDay 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 survivalDay 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

Safety and tolerability of the combination regimenDay 1 of treatment until 30 days post last dose

Toxicity analysis will be performed on a continual basis following CTC V 5.0 criteria

Trial Locations

Locations (2)

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Duke University

🇺🇸

Durham, North Carolina, United States

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