Non-small Cell Lung CancerPhase 2TOP1705NCT03573947
Phase II Clinical Trial of NIVO-IPI-TAXANE in Untreated Metastatic NSCLC
A Phase 2 study testing Nivolumab, Ipilimumab and Paclitaxel in people with Non-small Cell Lung Cancer, run by Jeffrey Clarke at 1 site in United States.
Trial summary
This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC. 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?
- Nivolumab, Ipilimumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2018to 15 Jun 2023
- 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 confirmed Stage IV or recurrent Non-small cell lung cancer squamous or non-squamous histology (Stage IV as diagnosed using the 7th edition of Lung Cancer Stage Classification), with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Prior adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy is permitted as long as the last administration of the prior regimen occurred at least 6 months prior to study enrollment. Patients with EGFR, ALK, or ROS1 alterations must have received one prior TKI.
- A core needle biopsy or surgical specimen must be available for submission.
- At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
- Age ≥ 18 years with ability and willingness to provide informed consent.
- ECOG performance status 0 or 1.
- Negative pregnancy test done ≤72 hours (or per institutional policy) prior to treatment, for women of childbearing potential only. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
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- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
- Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Men and women of childbearing potential must agree to use medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of study and for 90 days after the last dose of study drug.
- A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
- Provision of written informed consent including HIPAA according to institutional guidelines prior to any study-specific procedures
- Patients must agree to research blood sampling to participate in study;
- Adequate organ and marrow function as defined by the following:
- Creatinine clearance ≥ 50 cc/min or serum Cr < 1.5 x institutional ULN
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- AST/ALT ≤ 2 x ULN without liver metastasis; ≤ 5 x ULN with liver metastasis
- Absolute neutrophil count (ANC) ≥ 1500 µl
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100,000/µl
Who cannot join
- Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy and must have received treatment with at least one prior tyrosine kinase inhibitor (TKI).
- Subjects with known ALK or ROS1 translocations which are sensitive to available targeted inhibitor therapy must have received treatment with at least one prior TKI.
- Radiation therapy within 14 days prior to day 1 of study drug.
- Experimental agents within 28 days prior to day 1 of study drug.
- Intolerance of nivolumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
- Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone < 10 mg daily (or equivalent).
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- History of interstitial pneumonitis from any cause.
- Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
- Pregnant or breast feeding.
- Not willing to use an effective method of birth control medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug.
- Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to day 1 of study drug. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible.
- 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, or asymptomatic on cycle 1 day
- Steroid dose must be equivalent of <10 mg prednisone daily or equivalent dose steroid. Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.
- History of myocardial infarction, NYHA class III or IV congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.
- Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
- Inability to comply with protocol or study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase II Clinical Trial of Combination Nivolumab (Opdivo), Ipilimumab (Yervoy), and Paclitaxel in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (The OPTIMAL Trial) [TOP 1705]
This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC.
Read the detailed description
This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC.
Patients with histologically confirmed stage IV or recurrent non curable NSCLC of squamous or non-squamous histology, with no prior systemic anticancer chemotherapy or immunotherapy given as primary treatment for advanced or metastatic disease may be eligible to participate in this study.
Patients enrolled into the study will be given the study drugs, nivolumab (360 mg) (Day 1) every 3 weeks, ipilimumab 1 mg/kg (Day 1) every 6 weeks, and paclitaxel 80mg/m2 on days 1 and 8 of each 21- day study treatment cycle. Paclitaxel will be stopped after a total of 4-6 cycles of treatment. Blood samples and possibly a small piece of tissue may be removed the patient's lung to see what type of lung cancer cells that she or he may have. Patients will also have other tests, exams, and procedures for study purposes and their standard of care. Subject participation in the study will last for up to approximately 48 months after the start of the study drug or until their condition worsens or they experience intolerable adverse events as deemed by the study doctor.
There are possible patient risk to this study that include but are not limited to diarrhea, itching, rash and a feeling of weakness.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Nivolumab, Ipilimumab, Paclitaxel
- Keywords
- Stage IV Non-Small Cell Lung Cancer, nivolumab, ipilimumab, paclitaxel, immunotherapy
- 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.
NivolumabDrug
Also called Opdivo
360 mg intravenously every 3 weeks
IpilimumabDrug
Also called Yervoy
1 mg/kg intravenously over 30 minutes
PaclitaxelDrug
Also called Taxol
80 mg/m2 on days 1 and 8 of every 21-day treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| nivolumab, ipilimumab and paclitaxel | Experimental | patients will be treated with nivolumab and ipilimumab in combination with weekly paclitaxel days 1 and 8 every 21 days until they experience unacceptable drug-related toxicity, disease progression or 24 months.
The dosing regimen will be: nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and paclitaxel 80 mg/m2 on days 1 and 8 of 1 21 day treatment cycle. Paclitaxel would be stopped after a total of 4-6 cycles of treatment. Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (Brand Name) or Death, Whichever Occurs First
Progression-free survival (PFS) will be defined as the time from first dosing date to the date of the first documented tumor progression determined by the investigator using RECIST 1.1 or death, whichever occurs first
Measured: up to 4 years
Secondary outcomes (2)
Description of the Safety and Adverse Events of the Combination Nivolumab, Ipilimumab, and Paclitaxel in Untreated, Metastatic NSCLC.
The study will assess the number and percentage of participants who experience high grade (Grade 3-4 and Grade 5) treatment-related select and immune-mediated adverse events that include: pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, endocrinopathies, and hypersensitivity/infusion reaction events.
Measured: up to 4 years
Estimate the Overall Response Rate With the Study Combination.
Objective Response Rate (ORR) defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented tumor progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2018
- Study start2 Oct 2018
- Primary completion12 Mar 2023
- Study completion15 Jun 2023
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 Non-small Cell Lung CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Clarke
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jeffrey Clarke, Duke University
- Investigators
- Jeffrey Clarke, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03573947
- Sponsor's protocol ID
- Pro00092210
- Acronym
- TOP1705
- Status last verified
- Sep 2025
- First submitted
- 19 Jun 2018
- Last updated
- 14 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Combination Nivolumab (Opdivo), Ipilimumab (Yervoy), and Paclitaxel in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (The OPTIMAL Trial) [TOP 1705]
- ClinicalTrials.gov ID
- NCT03573947
- Acronym / sponsor ID
- TOP1705 / Pro00092210
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Stage IV Non-Small Cell Lung Cancer, nivolumab, ipilimumab, paclitaxel, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Jeffrey ClarkeUniversity, hospital or other
- Study start
- 2 Oct 2018 (actual)
- Primary completion
- 12 Mar 2023 (actual)
- Study completion
- 15 Jun 2023 (actual)
- First posted
- 29 Jun 2018 (actual)
- Results
- Posted 14 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC.
Detailed description
This is an open-label, non-randomized, phase II clinical research study designed to assess the safety and efficacy of nivolumab and ipilimumab in combination with paclitaxel in patients with treatment naïve NSCLC.
Patients with histologically confirmed stage IV or recurrent non curable NSCLC of squamous or non-squamous histology, with no prior systemic anticancer chemotherapy or immunotherapy given as primary treatment for advanced or metastatic disease may be eligible to participate in this study.
Patients enrolled into the study will be given the study drugs, nivolumab (360 mg) (Day 1) every 3 weeks, ipilimumab 1 mg/kg (Day 1) every 6 weeks, and paclitaxel 80mg/m2 on days 1 and 8 of each 21- day study treatment cycle. Paclitaxel will be stopped after a total of 4-6 cycles of treatment. Blood samples and possibly a small piece of tissue may be removed the patient's lung to see what type of lung cancer cells that she or he may have. Patients will also have other tests, exams, and procedures for study purposes and their standard of care. Subject participation in the study will last for up to approximately 48 months after the start of the study drug or until their condition worsens or they experience intolerable adverse events as deemed by the study doctor.
There are possible patient risk to this study that include but are not limited to diarrhea, itching, rash and a feeling of weakness.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| nivolumab, ipilimumab and paclitaxel | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Drug: Paclitaxelpatients will be treated with nivolumab and ipilimumab in combination with weekly paclitaxel days 1 and 8 every 21 days until they experience unacceptable drug-related toxicity, disease progression or 24 months. The dosing regimen will be: nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and paclitaxel 80 mg/m2 on days 1 and 8 of 1 21 day treatment cycle. Paclitaxel would be stopped after a total of 4-6 cycles of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed Stage IV or recurrent Non-small cell lung cancer squamous or non-squamous histology (Stage IV as diagnosed using the 7th edition of Lung Cancer Stage Classification), with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Prior adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy is permitted as long as the last administration of the prior regimen occurred at least 6 months prior to study enrollment. Patients with EGFR, ALK, or ROS1 alterations must have received one prior TKI.
- A core needle biopsy or surgical specimen must be available for submission.
- At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
- Age ≥ 18 years with ability and willingness to provide informed consent.
- ECOG performance status 0 or 1.
Key exclusion criteria (17 listed)
- Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy and must have received treatment with at least one prior tyrosine kinase inhibitor (TKI).
- Subjects with known ALK or ROS1 translocations which are sensitive to available targeted inhibitor therapy must have received treatment with at least one prior TKI.
- Radiation therapy within 14 days prior to day 1 of study drug.
- Experimental agents within 28 days prior to day 1 of study drug.
- Intolerance of nivolumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
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: Opdivo360 mg intravenously every 3 weeks | Drug | nivolumab, ipilimumab and paclitaxel |
| IpilimumabAlso: Yervoy1 mg/kg intravenously over 30 minutes | Drug | nivolumab, ipilimumab and paclitaxel |
| PaclitaxelAlso: Taxol80 mg/m2 on days 1 and 8 of every 21-day treatment cycle | Drug | nivolumab, ipilimumab and paclitaxel |
Primary outcome
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (Brand Name) or Death, Whichever Occurs First
Time frame: up to 4 years
Progression-free survival (PFS) will be defined as the time from first dosing date to the date of the first documented tumor progression determined by the investigator using RECIST 1.1 or death, whichever occurs first
2 secondary outcomes
Description of the Safety and Adverse Events of the Combination Nivolumab, Ipilimumab, and Paclitaxel in Untreated, Metastatic NSCLC.
Time frame: up to 4 years
Estimate the Overall Response Rate With the Study Combination.
Time frame: up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeffrey Clarke, 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 Paclitaxel in people with Non-small Cell Lung Cancer, run by Jeffrey Clarke 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 20 inclusion and 17 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: finished, as of the sponsor's last update on 14 Oct 2025. 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 14 Oct 2025). 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?
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (Brand Name) or Death, Whichever Occurs First (time frame: up to 4 years). 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 14 Oct 2025.