Clinical trial NCT05553834: PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC)
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2022-09-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Response rate associated with combination of alirocumab and cemiplimab
timeFrame: 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 outcomes:
measure: Safety and tolerability of the combination regimen
timeFrame: Day 1 of treatment until 30 days post last dose
measure: Progression Free Survival
timeFrame: Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks
measure: Overall survival
timeFrame: Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
References: