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

PRO00111111

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.

2023-05-16

2027-01-01

2029-01-01

Recruiting

Early phase I

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 60, 'type': 'ESTIMATED'}}

2024-05-24