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

• Sponsor: Duke University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05553834
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 25
• Arm: 1
• Anticipated Duration (Months): 69.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer (NSCLC)	Combination Product: Alirocumab and Cemiplimab	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Apr 1, 2023
• Anticipated Primary Completion Date: Jan 1, 2027
• Anticipated Study Completion Date: Jan 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alirocumab and Cemiplimab Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab	Combination Product: Alirocumab and Cemiplimab; Combination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks

Outcome Measures

Primary Outcome Measures

1. Response rate associated with combination of alirocumab and cemiplimab [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 Outcome Measures

1. Safety and tolerability of the combination regimen [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

2. Progression Free Survival [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

3. Overall survival [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Duke University
• Regeneron Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT05553834
• Other Study ID Numbers: PRO00111111
• First Posted: Sep 23, 2022
• Last Update Posted: Feb 1, 2023
• Last Verified: Sep 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cemiplimab

Study Results

No Results Posted as of Feb 1, 2023