Clinical trial · Interventional
PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Non-small Cell Lung Cancer (NSCLC) | Lung Non-Small Cell Carcinoma | ALIAS | 0.85 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Alirocumab and Cemiplimab | Combination Product | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Alirocumab and Cemiplimab
- description
- Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab
- interventionNames
- Combination Product: Alirocumab and Cemiplimab
Primary outcomes (1)
- 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
- description
- 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 outcomes (3)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDOduah EI, Zhang T, Jung SH, Stinchcombe TE, Ready N, Crawford J, Clarke JM, Gray JE, Antonia SJ. Alirocumab plus cemiplimab in advanced immuno-refractory metastatic non-small cell lung cancer: an ongoing multi-center phase II study. Future Oncol. 2026 Apr;22(9):1065-1072. doi: 10.1080/14796694.2026.2648863. Epub 2026 Apr 6. PMID 41940540