Lung Cancer MetastaticPhase 2TOP2101NCT05144529
A Randomized Pilot Study of Evolocumab Plus Nivolumab/Ipilimumab in Treatment-Naïve Patients With Metastatic NSCLC
A Phase 2 study testing Nivolumab, Ipilimumab and Evolocumab in people with Lung Cancer Metastatic, run by Eziafa Oduah, MD, PhD, MPH at 1 site in United States.
Trial summary
This is a research study to find out the safety and tolerability of combining the drug evolucumab with standard immunotherapy in people with advanced lung cancer (a type called non-small cell lung cancer). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer Metastatic
- What is being tested?
- Nivolumab, Ipilimumab and Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Mar 2022to 27 Sep 2024
- 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
- All patients must have histologically documented or suspected recurrent incurable and/or stage 4 squamous or non-squamous NSCLC.
- NO prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis recurrent/metastatic NSCLC. Medical therapy (including adjuvant or maintenance immune therapy) for early stage NSCLC allowed if completed > 6 months prior to study enrollment.
- TPS PD-L1 < 50%
- Performance Status ECOG 0-1 (Appendix B).
- Age >18 years old.
- No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
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- No autoimmune disease that would constitute contraindication to receive nivolumab
- Patients must have core needle biopsy tissue that is available and adequate for dedicated research purposes.
- No excessive risk for CT or ultrasound guided percutaneous biopsy to obtain research biopsy specimen. Risk assessment is to be determined by the treating oncologist and the interventional radiologist.
- Patients who do not have an indication for a diagnostic biopsy must undergo an elective 'research only' core needle biopsy.
- Signed written informed consent including HIPAA according to institutional guidelines.
- Safety laboratory values within institutional normal ranges.
Who cannot join
- 1) Is 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 treatment.
- 2) Has a known history of active TB (Bacillus Tuberculosis) 3) Hypersensitivity to nivolumab or ipilimumab or any of its excipients 4) Hypersensitivity to evolocumab or any of its excipients 5) Patient does not have a site of suspected malignancy that is accessible to pre-treatment biopsy.
- 6) Concurrent administration of any other anti-tumor therapy. 7) Has received prior therapy with a PD1, PDL1, or PDL2 inhibitor. 8) Has received therapy with PCSK9 inhibitor within 90 days of study entry. 9) Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to cycle 1 day 1, are clinically controlled, and asymptomatic off high dose steroids on cycle 1 day 1(< 2 mg decadron or 10 mg prednisone daily or equivalent allowed). Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.
- 10) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- 11) Inability to comply with protocol or study procedures. 12) Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- 13) Has known history of, or any evidence of active, non-infectious pneumonitis.
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- 14) Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) 15) Has 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 system 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 [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- 16) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity 17) Has a 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 trial treatment.
- 18) Is 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 trial treatment.
- 19) 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 of compromise the patient's ability to complete the study.
- 20) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 30 days before or after any dose of nivolumab). 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. COVID19 vaccines will be allowed on protocol.
- 21) Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications. Patients with CAD recently treated with surgery and/or stent, if stable without symptomatic angina pectoris, active ischemia are eligible.
- 22) Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 23) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either psychiatric or physical (e.g., infectious) illness.
- 24) Patient takes daily prednisone > 10 mg or the equivalent dose of a different steroid.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Univ. Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Randomized Pilot Study to Investigate the Safety and Immunologic Impact of Evolocumab When Given in Combination With Ipilimumab and Nivolumab in Treatment-Naïve Patients With Metastatic Non-Small Cell Lung Cancer
This is a research study to find out the safety and tolerability of combining the drug evolucumab with standard immunotherapy in people with advanced lung cancer (a type called non-small cell lung cancer).
Nivolumab (Opdivo™) and ipilimumab (Yervoy™) are immunotherapy-type drugs which are approved for the treatment of advanced lung cancer that has expression of PD-L1 greater than or equal to 1%. Evolucumab is being combined with nivolumab and ipilimumab to see if it will improve the anti-tumor capabilities of the immunotherapy. Adding evolocumab to the combination of nivolumab and ipilimumab has not been tested in people before and is considered investigational.
- Conditions
- Lung Cancer Metastatic
- Being tested
- Nivolumab, Ipilimumab, Evolocumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab IV 240 mg
IpilimumabDrug
Also called Yervoy
Ipilimumab IV 1 mg/kg
EvolocumabDrug
Also called Repatha
Evolocumab 14 mg subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab/nivolumab | Active comparator | Subjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks. Receives: Drug: Nivolumab; Drug: Ipilimumab |
| ipilimumab/nivolumab/evolucumab | Experimental | Subjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks plus evolocumab 140 mg SC every 2 weeks Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With DLT (Dose-limiting Toxicity)
Safety is defined as the incidence of DLTs assessed in the first 6 evaluable subjects treated with nivolumab, ipilimumab, and evolocumab, including those that cross over to receive evolocumab.
Measured: Up to 30 days after first study dose
Change in CD3+ Tumor Infiltrating Lymphocytes
To characterize treatment-related changes in tumor infiltrating lymphocytes (TIL) using immunohistochemistry analysis. The mean and the standard deviation of the pre-treatment CD3+ TILs and the on-treatment CD3+ TILS as well as those of the difference of these ratios will be estimated.
Measured: Baseline and day 29
Secondary outcomes (4)
Change in MHC-1 Expression
To assess the change in the degree of surface expression of MHC-I molecules on tumor cells within each patient comparing on-treatment versus pre-treatment biopsy specimens.
Measured: Baseline and day 29
Progression-free Survival (PFS)
PFS is defined as the time between initiation of treatment and initial failure (disease progression or death), whichever comes first.
Measured: Up to 2 years
Overall Survival (OS)
OS is defined as the time from the first dose of study treatment to death.
Measured: Up to 2 years
Objective Response Rate (ORR)
Response rate is defined as the percentage of treated subjects with a complete or partial response
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2021
- Study start22 Mar 2022
- Primary completion27 Sep 2024
- Study completion27 Sep 2024
Why it stopped: Slow enrollment.
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.
- Other trials for Lung Cancer MetastaticStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eziafa Oduah, MD, PhD, MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Eziafa Oduah, MD, PhD, MPH, Duke University
- Investigators
- Scott Antonia, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05144529
- Sponsor's protocol ID
- Pro00109594
- Other IDs
- W81XWH-21-1-0532
- Acronym
- TOP2101
- Status last verified
- Apr 2026
- First submitted
- 22 Nov 2021
- Last updated
- 5 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pilot Study to Investigate the Safety and Immunologic Impact of Evolocumab When Given in Combination With Ipilimumab and Nivolumab in Treatment-Naïve Patients With Metastatic Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05144529
- Acronym / sponsor ID
- TOP2101 / Pro00109594
- Conditions
- Lung Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Eziafa Oduah, MD, PhD, MPHUniversity, hospital or other
- Study start
- 22 Mar 2022 (actual)
- Primary completion
- 27 Sep 2024 (actual)
- Study completion
- 27 Sep 2024 (actual)
- First posted
- 3 Dec 2021 (actual)
- Results
- Posted 5 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study to find out the safety and tolerability of combining the drug evolucumab with standard immunotherapy in people with advanced lung cancer (a type called non-small cell lung cancer).
Nivolumab (Opdivo™) and ipilimumab (Yervoy™) are immunotherapy-type drugs which are approved for the treatment of advanced lung cancer that has expression of PD-L1 greater than or equal to 1%. Evolucumab is being combined with nivolumab and ipilimumab to see if it will improve the anti-tumor capabilities of the immunotherapy. Adding evolocumab to the combination of nivolumab and ipilimumab has not been tested in people before and is considered investigational.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab/nivolumab | Active comparator | Drug: Nivolumab, Drug: IpilimumabSubjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks. |
| ipilimumab/nivolumab/evolucumab | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Drug: EvolocumabSubjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks plus evolocumab 140 mg SC every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- All patients must have histologically documented or suspected recurrent incurable and/or stage 4 squamous or non-squamous NSCLC.
- NO prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis recurrent/metastatic NSCLC. Medical therapy (including adjuvant or maintenance immune therapy) for early stage NSCLC allowed if completed > 6 months prior to study enrollment.
- TPS PD-L1 < 50%
- Performance Status ECOG 0-1 (Appendix B).
- Age >18 years old.
Key exclusion criteria (15 listed)
- 1) Is 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 treatment.
- 2) Has a known history of active TB (Bacillus Tuberculosis) 3) Hypersensitivity to nivolumab or ipilimumab or any of its excipients 4) Hypersensitivity to evolocumab or any of its excipients 5) Patient does not have a site of suspected malignancy that is accessible to pre-treatment biopsy.
- 6) Concurrent administration of any other anti-tumor therapy. 7) Has received prior therapy with a PD1, PDL1, or PDL2 inhibitor. 8) Has received therapy with PCSK9 inhibitor within 90 days of study entry. 9) Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to cycle 1 day 1, are clinically controlled, and asymptomatic off high dose steroids on cycle 1 day 1(< 2 mg decadron or 10 mg prednisone daily or equivalent allowed). Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.
- 10) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- 11) Inability to comply with protocol or study procedures. 12) Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate 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 |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab IV 240 mg | Drug | Ipilimumab/nivolumab, ipilimumab/nivolumab/evolucumab |
| IpilimumabAlso: YervoyIpilimumab IV 1 mg/kg | Drug | Ipilimumab/nivolumab, ipilimumab/nivolumab/evolucumab |
| EvolocumabAlso: RepathaEvolocumab 14 mg subcutaneous injection | Drug | ipilimumab/nivolumab/evolucumab |
Primary outcome
Number of Participants With DLT (Dose-limiting Toxicity)
Time frame: Up to 30 days after first study dose
Safety is defined as the incidence of DLTs assessed in the first 6 evaluable subjects treated with nivolumab, ipilimumab, and evolocumab, including those that cross over to receive evolocumab.
Change in CD3+ Tumor Infiltrating Lymphocytes
Time frame: Baseline and day 29
To characterize treatment-related changes in tumor infiltrating lymphocytes (TIL) using immunohistochemistry analysis. The mean and the standard deviation of the pre-treatment CD3+ TILs and the on-treatment CD3+ TILS as well as those of the difference of these ratios will be estimated.
4 secondary outcomes
Change in MHC-1 Expression
Time frame: Baseline and day 29
Progression-free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Objective Response Rate (ORR)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Scott Antonia, MD 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 Nivolumab, Ipilimumab and Evolocumab in people with Lung Cancer Metastatic, run by Eziafa Oduah, MD, PhD, MPH 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 12 inclusion and 15 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: stopped early, as of the sponsor's last update on 5 May 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?
Yes. Results are posted in the registry (first posted 5 May 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 DLT (Dose-limiting Toxicity) (time frame: Up to 30 days after first study dose). 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 5 May 2026.