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Non-small Cell Lung CancerPhase 2NCT03285321

Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC)

A Phase 2 study testing Nivolumab and Ipilimumab in people with Non-small Cell Lung Cancer, run by Greg Durm, MD at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is an open label, multicenter, randomized phase II trial of consolidation immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab following concurrent chemoradiation in patients with unresectable stage III 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 and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
12 sitesUnited States
Study dates
15 Sep 2017to 6 Feb 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

  • Subject must meet all of the following applicable inclusion criteria to participate in this study:
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0 or 1 within 14 days prior to registration.
  • Histological or cytological confirmation of NSCLC. A pathology report confirming the diagnosis of NSCLC must be obtained and reviewed by the treating physician prior to registration to study.
  • Must have unresectable or inoperable stage IIIA or IIIB disease according to the 7th edition IASLC stage classification for lung cancer. Subjects must be considered unresectable or inoperable based on the judgment of the treating physician.
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  • Subjects must have completed concurrent chemoradiation with a platinum doublet and a dose of radiation ranging from 59.4-66.6 Gy. Subjects must have stable disease or disease response as evidenced on CT or PET scan evaluation. For those eligible, protocol therapy should begin within 56 days of completing chemoradiation OR Subjects must have completed up to 2 cycles of consolidation therapy started within 56 days of completion of radiation. After completion of consolidation chemotherapy, subjects must have stable disease or disease response as evidenced by CT or PET scan evaluation. For those eligible, protocol therapy should begin within 56 days after the last cycle of chemotherapy.
  • Prior cancer treatment must be completed between 1-56 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
  • Demonstrate adequate organ function, all screening labs to be obtained within 14 days prior to registration:
  • Hematological:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm^3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelets ≥100,000/mcl
  • Renal:
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min for subjects with creatinine levels >1.5 x institutional ULN
  • Hepatic:
  • Bilirubin ≤ 1.5 × ULN OR Direct bilirubin of ≤ ULN for subjects with total bilirubin levels of >1.5x ULN
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN
  • Coagulation:
  • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT/INR/PTT is within therapeutic range of intended use of anticoagulants
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration. NOTE: Women are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be considered post-menopausal.
  • Women of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 23 weeks after treatment discontinuation.
  • Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drug and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Subjects meeting any of the criteria below may not participate in the study:
  • 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 23 weeks (female) or 31 weeks (male) after the last dose of trial treatment.
  • Active central nervous system (CNS) metastases. Subjects must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging.
  • Treatment with any investigational agent within 28 days prior to registration for protocol therapy.
  • Prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer other than standard concurrent chemoradiation or up to 2 cycles of consolidation.
  • Prior therapy with a PD-1, PD-L1, PD-L2 or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy.
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  • Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be evaluated with a CT or PET scan prior to registration for protocol therapy to exclude metastatic disease.
  • Active second cancers.
  • Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
  • Interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
  • Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of first dose of study drug.
  • History of psychiatric illness or social situations that would limit compliance with study requirements.
  • Clinically active infection as judged by the site investigator (≥ Grade 2 by CTCAE v4).
  • History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Hypersensitivity to nivolumab, ipilimumab, or any of their excipients.
  • Has received a live vaccine within 30 days prior to planned start of study therapy. 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.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • Johns Hopkins Sidney Kimmel Comprehensive

    Baltimore, Maryland, 21287

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612

  • Karmanos Cancer Center (Wayne State University)

    Detroit, Michigan, 48201

  • Penn State Cancer Institute

    Hershey, Pennsylvania, 17033

  • Indiana University

    Indianapolis, Indiana, 46202

  • Michigan State University

    Lansing, Michigan, 48910

  • University of Louisville James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • University of Wisconsin

    Madison, Wisconsin, 53705

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: Phase II Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC): BTCRC-LUN16-081

This study is an open label, multicenter, randomized phase II trial of consolidation immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab following concurrent chemoradiation in patients with unresectable stage III NSCLC.

Read the detailed description

Patients with unresectable stage IIIA or IIIB NSCLC (unresectable as defined by treating physician) will be treated outside this study with concurrent chemoradiation with one of three chemotherapy regimens (cisplatin/etoposide, cisplatin/pemetrexed, or weekly carboplatin/paclitaxel) in addition to standard dose radiation (dosing can range from 59.4 Gy to 66.6 Gy). If repeat imaging between 28-56 days following completion of chemoradiation shows no progressive or metastatic disease, the patients will be eligible for enrollment on the study.

Randomization and Stratification:

At the time of enrollment, patients will be randomized in a 1:1 fashion to receive either nivolumab 480mg IV every 4 weeks or the combination of nivolumab 3mg/kg IV every 2 weeks with ipilimumab 1mg/kg IV every 6 weeks. Consolidation immunotherapy will be continued until progression or unacceptable toxicity for up to a total of 24 weeks.

Subjects will be stratified by stage (IIIA vs. IIIB) and histology (squamous vs. non-squamous).

Dose Calculations:

Arm 1: The dose of nivolumab will be a fixed dose (not based on subject's weight) at 480mg.

Arm 2: The dose of nivolumab will be weight-based at 3mg/kg. The dose of ipilimumab will be weight-based at 1mg/kg.

Nivolumab Alone (Arm 1):

Arm 1: Nivolumab Administration:

Nivolumab 480 mg will be administered as a 60 minute IV infusion on Day 1 of each 28 day cycle. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 6 cycles, in the absence of prohibitive toxicities or disease progression.

Nivolumab Plus Ipilimumab (Arm 2):

Arm 2: Nivolumb Administration:

Nivolumab 3mg/kg will be administered as a 60 minute IV infusion on Day 1, 15, and 29 of each 42 day cycle. Nivolumab should not be given any earlier than 12 days from the previous dose. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression.

Arm 2: Ipilimumab Administration:

Ipilimumab 1mg/kg will be administered as a 90 minute IV infusion on Day 1 of each 42 day cycle. Sites should make every effort to target infusion timing to be as close to 90 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression.

On day 1 of cycle 1, nivolumab will be given first, followed by 30 minutes of monitoring, and then ipilimumab given second, followed by 30 minutes of monitoring. If the subject does not have an infusion reaction during the first cycle, the post-ipilimumab monitoring may be discontinued for subsequent cycles at the discretion of the treating physician. Day 1 monitoring between the nivolumab/ipilimumab infusions will continue throughout all 4 cycles. Post nivolumab monitoring on days 15 and 29 is not mandatory and should follow the guidelines of the local infusion center.

Being tested
Nivolumab, Ipilimumab
Keywords
Nivolumab, Ipilimumab, 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.

Study groups in NCT03285321
Study groupRoleWhat they receive
Arm 1ExperimentalNivolumab 480mg IV every 4 weeks for up to 6 cycles
Receives: Drug: Nivolumab
Arm 2ExperimentalNivolumab 240mg IV every 2 weeks PLUS Ipilimumab 1mg/kg IV every 6 weeks for up to 4 cycles (12 doses Nivolumab and 4 doses of Ipilimumab)
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) at 18-month

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

    PFS is defined as the time from randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.

    Measured: 18 months

Secondary outcomes (3)
  1. Overall Survival (OS)

    Overall survival is defined as the time from randomization until death from any cause.

    Measured: 4 years

  2. Time to Metastatic Disease (TTMD) at 36 Month

    TTMD is defined as the time from randomization until evidence of disease outside of the radiated field. The estimate of TTMD at 36 month with 95% confidence interval are reported in the outcome measure data.

    Measured: 36 Months

  3. Number of Participants With Adverse Events

    Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2017
  2. Study start15 Sep 2017
  3. Primary completion13 Oct 2023
  4. Study completion6 Feb 2024

Resources

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
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03285321
Sponsor's protocol ID
BTCRC-LUN16-081
Status last verified
Dec 2025
First submitted
14 Sep 2017
Last updated
20 Jan 2026
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Jun S, Shukla NA, Durm G, Hui AB, Cao S, Ganti AK, Jabbour SK, Kunder C, Alizadeh AA, Hanna NH, Diehn M. Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC. J Thorac Oncol. 2024 Oct;19(10):1427-1437. doi: 10.1016/j.jtho.2024.06.024. Epub 2024 Jul 5.

    PubMed 38971369

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Non-small Cell Lung Cancer, run by Greg Durm, MD at 12 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 25 inclusion and 18 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 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 11 Mar 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) at 18-month (time frame: 18 months). 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 NCT03285321, 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 20 Jan 2026.

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