Non-small Cell Lung Cancer (NSCLC)Phase 2NCT05553834
PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung
A Phase 2 study testing Alirocumab and Cemiplimab in people with Non-small Cell Lung Cancer (NSCLC), run by Duke University at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Alirocumab and Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 May 2023to 1 Nov 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University
Durham, North Carolina, 27705
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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
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
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- Alirocumab and Cemiplimab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alirocumab and CemiplimabCombination product
Combination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alirocumab and Cemiplimab | Experimental | Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab Receives: Combination Product: Alirocumab and Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Complete or Partial Response (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 Criteria
A partial response (PR) under RECIST 1.1 guidelines indicates there is at least a 30% decrease in the sum of the longest diameters of target tumors, compared to the baseline measurement.
Measured: 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 (3)
Number of Participants Who Experienced an Adverse Event
A measurement of the safety and tolerability of the combination regimen. Toxicity analysis will be performed on a continual basis following CTC V 5.0 criteria.
Measured: Day 1 of treatment until 30 days post last day of treatment for up to 2 years of treatment duration or when patient comes off treatment earlier than 2 years due to any other reason
Progression Free Survival (PFS) Per RECIST 1.1. Criteria
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or unequivocal progression of non-target lesion(s), or the appearance of new lesion(s), or death
Measured: Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks
Overall Survival (OS)
Overall survival (OS) is the length of time that participants remain alive.
Measured: Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start16 May 2023
- Primary completion16 Sep 2025
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05553834
- Sponsor's protocol ID
- PRO00111111
- Status last verified
- Oct 2026
- First submitted
- 2 Sep 2022
- Last updated
- 4 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Oduah 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.
PubMed 41940540
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05553834
- Acronym / sponsor ID
- PRO00111111
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 16 May 2023 (actual)
- Primary completion
- 16 Sep 2025 (actual)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 23 Sep 2022 (actual)
- Results
- Posted 4 Nov 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Combination therapy involving anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab.
| Arm | Type | Receives |
|---|---|---|
| Alirocumab and Cemiplimab | Experimental | Combination Product: Alirocumab and CemiplimabCombination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alirocumab and CemiplimabCombination of PCSK9 inhibitor Alirocumab 150mg SC q2weeks and PD-I inhibitor Cemiplimab 350mg IV q3 weeks | Combination product | Alirocumab and Cemiplimab |
Primary outcome
Number of Participants With a Complete or Partial Response (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 Criteria
Time frame: 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
A partial response (PR) under RECIST 1.1 guidelines indicates there is at least a 30% decrease in the sum of the longest diameters of target tumors, compared to the baseline measurement.
3 secondary outcomes
Number of Participants Who Experienced an Adverse Event
Time frame: Day 1 of treatment until 30 days post last day of treatment for up to 2 years of treatment duration or when patient comes off treatment earlier than 2 years due to any other reason
Progression Free Survival (PFS) Per RECIST 1.1. Criteria
Time frame: Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks
Overall Survival (OS)
Time frame: Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41940540Oduah 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alirocumab and Cemiplimab in people with Non-small Cell Lung Cancer (NSCLC), run by Duke University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Complete or Partial Response (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 Criteria (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05553834, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.