Non Small Cell Lung CancerPhase 2NCT06385262
TOP 2301: Neoadjuvant Chemo for NSCLC
A Phase 2 study testing Alirocumab, Cemiplimab and Chemotherapy in people with Non Small Cell Lung Cancer, run by Duke University at 1 site in United States.
Trial summary
This study was originally opened on 10/22/2024 as an open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) to receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Alirocumab, Cemiplimab and Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2025to 30 Oct 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years.
- Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Patient is eligible to enroll in the study based on clinical suspicion of NSCLC but are required to have a histological diagnosis of NSCLC in order to be eligible to receive treatment on study.
- Clinical stage IB, IIA/IIB, or III (N0-2) amenable to surgical resection.
- Agrees to research blood collections for study.
- Deemed a surgical candidate.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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- No prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer.
- Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
- Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines.
- Sexually active males and females of reproductive potential must agree to use an appropriate contraceptive method during the study and for 120 days following the last dose of study drug.
- Females of childbearing potential must test negative for pregnancy within 48 hours prior to any initial study procedure based on a serum pregnancy test. (If subject uses appropriate contraceptive methods from the time of the initial serum pregnancy test, then the subsequent pregnancy test can be done within 72 hours prior to start of study treatment. If appropriate contraceptive measures are not begun immediately with the first serum pregnancy test, then subsequent serum pregnancy tests must be done within 48 hours prior to the start of study treatment.)
- Adequate organ function defined as:
- Absolute neutrophil count (ANC) ≥ 1500 per uL
- Platelets ≥ 100,000 per uL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or growth factor dependency (within 7 days of assessment)
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 60 mL/min for subject with creatinine levels > 1.5 x ULN
- Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase (SGOT)] and alanine aminotransferase (ALT) [glutamic-pyruvic transaminase (SGPT)]≤ 2.5 x ULN
- Albumin ≥ 2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants
Who cannot join
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
- Participants with known EGFR mutations, ALK translocation, or ROS1 translocation. If testing is done, an FDA-approved assay should be used.
- Known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to alirocumab or any of its excipients.
- Concurrent administration of any other anti-tumor therapy.
- Prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent.
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- Therapy with an anti-PCSK9 agent within 90 days of study entry.
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Inability to comply with protocol or study procedures.
- Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or HCV infection; or diagnosis of immunodeficiency. Exceptions:
- Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
- Patients with HBV (hepatitis B surface antigen positive) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted.
- Patients who are HCV antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc.) is not considered a form of systemic treatment. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g. Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Known additional invasive malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy in situ cervical cancer.
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
- Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant disorders that in the opinion of the investigator would compromise the safety of the patient or compromise the patient's ability to complete the study.
- Any non-oncology, live vaccine therapy used for prevention of infectious diseases within 30 days prior to start of study treatment.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. Coronavirus Disease 2019 (COVID-19) vaccines are also allowed.
- Myocardial infarction having occurred less than 6 months prior to study enrollment, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications. Patients with coronary artery disease treated with surgery and/or stent > 6 months ago, if stable without symptomatic angina pectoris, active ischemia are eligible.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either psychiatric or physical (e.g., infectious) illness.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University
Durham, North Carolina, 27710
Neal Ready, MD, 9196816932, neal.ready@duke.edu
Monika Anand, PhD, 7329106733, monika.anand@duke.edu
About this study
Official title: Safety, Efficacy, and Tumor Immune Microenvironment Changes With Neoadjuvant Chemotherapy and Cemiplimab With or Without Alirocumab in Stage 1B-3A Non-Small Cell Lung Cancer: TOP 2301
This study was originally opened on 10/22/2024 as an open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) to receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. As of 7/20/2026, the study was amended to a single arm receiving neoadjuvant chemotherapy, cemiplimab every 3 weeks for 3 cycles and alirocumab every 4 weeks prior to surgery.
The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Alirocumab, Cemiplimab, Chemotherapy
- 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.
AlirocumabDrug
300 mg subcutaneously every 4 weeks prior to surgery
CemiplimabDrug
350mg IV every 3 weeks prior to surgery
ChemotherapyDrug
Treating provider's choice of FDA approved platinum doublet chemotherapy IV every 3 weeks prior to surgery
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles with alirocumab (PCSK9 inhibitor) every 4 weeks prior to surgery. Receives: Drug: Alirocumab; Drug: Cemiplimab; Drug: Chemotherapy |
| Arm B | Experimental | Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles without alirocumab (PCSK9 inhibitor) prior to surgery.
This ARM was closed as of 7/20/2026 Receives: Drug: Cemiplimab; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the pathologic complete response (pCR) rate for neoadjuvant chemotherapy plus cemiplimab with alirocumab.
Pathologic complete response (pCR) is defined as a lack of all signs of cancer in tissue samples removed during surgery or biopsy after neoadjuvant therapy.
Measured: 2 years
Determine the safety, and tolerability of neoadjuvant chemotherapy and cemiplimab with alirocumab in early-stage non-small cell lung cancer
Safety will be determined by evaluating the severe adverse events rate for the experimental therapy.
Measured: 2 years
Secondary outcomes (6)
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Objective Response Rate (ORR)
ORR is defined as Complete Response (CR) + Partial Response (PR) as determined per RECIST 1.1 for the surgical outcome
Measured: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Disease Control Rate (SD)
Disease Control Rate (SD) is defined as the time from treatment initiation to disease progression (first disease recurrence or death, whichever comes first) after surgery
Measured: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Duration of Response (DOR)
Duration of Response (DOR) is defined as the time from treatment initiation to disease recurrence (first disease recurrence or death, whichever comes first) after surgery
Measured: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Event Free Survival (EFS)
Event Free Survival (EFS) is defined as the time from study enrollment to event recurrence (first disease progression or death, whichever comes first) after surgery
Measured: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Major Pathologic Response (MPR)
Major Pathologic Response (MPR) is determined by calculating percentage of viable tumor cells in the resected tumor
Measured: Surgery
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by overall survival (OS)
Overall survival (OS) is the length of time that a patient lives following treatment
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2024
- Study start17 Mar 2025
- Primary completion30 Oct 2028 (estimated)
- Study completion30 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Principal investigator, Neal Ready MD PhD, Duke University
- Investigators
- Neal Ready, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06385262
- Sponsor's protocol ID
- Pro00114645
- Status last verified
- Aug 2026
- First submitted
- 22 Apr 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Efficacy, and Tumor Immune Microenvironment Changes With Neoadjuvant Chemotherapy and Cemiplimab With or Without Alirocumab in Stage 1B-3A Non-Small Cell Lung Cancer: TOP 2301
- ClinicalTrials.gov ID
- NCT06385262
- Acronym / sponsor ID
- Pro00114645
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 17 Mar 2025 (actual)
- Primary completion
- 30 Oct 2028 (estimated)
- Study completion
- 30 Oct 2029 (estimated)
- First posted
- 26 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was originally opened on 10/22/2024 as an open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) to receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. As of 7/20/2026, the study was amended to a single arm receiving neoadjuvant chemotherapy, cemiplimab every 3 weeks for 3 cycles and alirocumab every 4 weeks prior to surgery.
The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Alirocumab, Drug: Cemiplimab, Drug: ChemotherapyChemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles with alirocumab (PCSK9 inhibitor) every 4 weeks prior to surgery. |
| Arm B | Experimental | Drug: Cemiplimab, Drug: ChemotherapyChemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles without alirocumab (PCSK9 inhibitor) prior to surgery. This ARM was closed as of 7/20/2026 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Age ≥ 18 years.
- Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Patient is eligible to enroll in the study based on clinical suspicion of NSCLC but are required to have a histological diagnosis of NSCLC in order to be eligible to receive treatment on study.
- Clinical stage IB, IIA/IIB, or III (N0-2) amenable to surgical resection.
- Agrees to research blood collections for study.
- Deemed a surgical candidate.
Key exclusion criteria (25 listed)
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
- Participants with known EGFR mutations, ALK translocation, or ROS1 translocation. If testing is done, an FDA-approved assay should be used.
- Known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to alirocumab or any of its excipients.
- Concurrent administration of any other anti-tumor therapy.
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 |
|---|---|---|
| Alirocumab300 mg subcutaneously every 4 weeks prior to surgery | Drug | Arm A |
| Cemiplimab350mg IV every 3 weeks prior to surgery | Drug | Arm A, Arm B |
| ChemotherapyTreating provider's choice of FDA approved platinum doublet chemotherapy IV every 3 weeks prior to surgery | Drug | Arm A, Arm B |
Primary outcome
Evaluate the pathologic complete response (pCR) rate for neoadjuvant chemotherapy plus cemiplimab with alirocumab.
Time frame: 2 years
Pathologic complete response (pCR) is defined as a lack of all signs of cancer in tissue samples removed during surgery or biopsy after neoadjuvant therapy.
Determine the safety, and tolerability of neoadjuvant chemotherapy and cemiplimab with alirocumab in early-stage non-small cell lung cancer
Time frame: 2 years
Safety will be determined by evaluating the severe adverse events rate for the experimental therapy.
6 secondary outcomes
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Objective Response Rate (ORR)
Time frame: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Disease Control Rate (SD)
Time frame: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Duration of Response (DOR)
Time frame: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Event Free Survival (EFS)
Time frame: 2 years
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by Major Pathologic Response (MPR)
Time frame: Surgery
Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by overall survival (OS)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- 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.
Neal Ready, MD, PhD principal investigator
Duke University
1 site 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, Cemiplimab and Chemotherapy in people with Non Small Cell Lung Cancer, run by Duke University at 1 site 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 22 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Neal Ready, MD, PhD (+1 919 681 6932, neal.ready@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the pathologic complete response (pCR) rate for neoadjuvant chemotherapy plus cemiplimab with alirocumab. (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2026.