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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05553834
• Other study ID #: PRO00111111
• Status: Recruiting
• Phase: Phase 2
• Start date: May 16, 2023
• Est. completion date: January 1, 2029

Study information

• Verified date: May 2024
• Source: Duke University
• Contact: Scott Antonia, MD
• Phone: 919 681 9509
• Email: scott.antonia[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

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

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate associated with combination of alirocumab and cemiplimab	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	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
Secondary	Safety and tolerability of the combination regimen	Toxicity analysis will be performed on a continual basis following CTC V 5.0 criteria	Day 1 of treatment until 30 days post last dose
Secondary	Progression Free Survival	Progression Free Survival will be assessed utilizing RECIST 1.1 criteria	Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks
Secondary	Overall survival	Patients will be followed till death or off study due to any other reason	Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks