Non-small Cell Lung Cancer (NSCLC)
Conditions
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.
Interventions
COMBINATION_PRODUCTAlirocumab and Cemiplimab
Combination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks
Sponsors
Duke University
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed