First-Line Ipilimumab Plus Nivolumab and Nogapendekin Alfa Inbakicept (N-803) in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
A Phase Ib/II, Single-Center, Open-Label Study of First-Line Ipilimumab Plus Nivolumab and Nogapendekin Alfa Inbakicept (N-803) in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer (FLINN)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether adding nogapendekin alfa inbakicept (N-803) helps nivolumab and ipilimumab work better. It is for adults with non-small cell lung cancer that has spread or come back.
This is a single center, phase Ib/II study combining an anti-PD-1 antibody and an anti-CTLA-4 antibody with IL-15. It is testing the hypothesis that the addition of nogapendekin alfa inbakicept to nivolumab and ipilimumab will augment the clinical activity of those two drugs.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older, with non-small cell lung cancer confirmed by a tissue or cell test. The cancer must be untreated or have come back and spread.
- Have cancer that can be measured on scans.
- Have stored tumor tissue available, or agree to a biopsy before treatment to collect tissue for testing.
- Be fully active or able to do light work despite some limits on hard physical activity.
- Have blood tests showing that blood cell levels, liver function, kidney function, and blood clotting meet study limits.
- If cancer has spread to the brain, it must have been treated with surgery or radiation. Symptoms must be stable after at least 2 weeks, with no more than 10 mg of prednisone or a similar steroid daily when study treatment starts.
- If able to become pregnant or father a child, agree to use highly effective birth control from consent until 6 months after the last study dose.
- Be able and willing to give written consent. A legally authorized representative may give consent for you.
Who can't join
- Cancer that includes small cell lung cancer, or has certain gene changes: classic EGFR mutations, HER2 mutations, ALK, ROS1, RET or NTRK fusions, MET exon 14 skipping, or BRAF V600E.
- Recent treatments: a live vaccine within 28 days; chemotherapy after surgery or with radiation for locally advanced cancer within 12 months; radiation or major surgery within 14 days; or another experimental drug within 28 days or 5 drug half-lives, whichever is longer. A half-life is the time for half a drug to leave the body.
- A condition that makes treatment unsafe or side effects hard to judge. Examples include lung scarring or noninfectious lung inflammation, serious heart disease, a past organ transplant, or an infection needing injected treatment within 14 days.
- A condition needing more than 10 mg of prednisone daily or other drugs that weaken the immune system. Long-term steroids that affect the whole body are also excluded.
- Active autoimmune disease, where the immune system attacks the body, or a history of it needing whole-body treatment in the past 2 years. Exceptions include vitiligo, resolved childhood asthma or allergies, hormone replacement, and certain occasional asthma treatments.
- HIV without effective treatment and undetectable virus levels for at least 6 months; hepatitis B still detectable during treatment; or hepatitis C that is not cured, unless treatment has made virus levels undetectable.
- A mental health or substance use condition that prevents following study rules; another cancer that could affect study safety or results; or a known allergy to study drugs, similar substances, or their ingredients.
- Pregnancy or breastfeeding. Anyone able to become pregnant must have a negative pregnancy test within 7 days before joining.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Histologically or cytologically confirmed, previously untreated or recurrent metastatic NSCLC. * Availability of archival biopsy tissue or willingness to undergo a biopsy prior to C1D1 for biomarker analysis, including PD-L1 by IHC using a CLIA-certified test. Results of the PD-L1 testing are not required for enrollment. * Measurable disease per RECIST 1.1. * At least 18 years of age. * ECOG performance status ≤ 1 * Adequate organ and marrow function, as defined below: * Absolute neutrophil count ≥ 1.5 K/cumm * Platelets ≥ 100 K/cumm * Hemoglobin ≥ 9.0 g/dL * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5 x IULN with hepatic metastasis * Total bilirubin ≤ 2 x IULN (except participants with Gilbert's syndrome who must have total bilirubin \< 3.0 mg/dL) * Creatinine clearance \> 30 mL/min by Cockcroft-Gault * INR ≤ 1.5 unless using therapeutic anticoagulation * PTT/aPTT \< 1.5 x IULN unless using therapeutic anticoagulation * Patients with brain metastases are eligible if they have previously treated with surgery or radiation therapy, are neurologically stable after a washout period of at least 2 weeks, and are not receiving corticosteroids at dose higher than 10 mg of prednisone or equivalent on C1D1. * The effects of the treatment regimen on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use highly effective methods of contraception, according to the protocol, from the time of consent through 6 months after the last dose of study treatment. * Ability to understand and willingness to sign an IRB-approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. Exclusion Criteria: * Mixed histology including small cell lung cancer. * Tumor harboring any of the following: * classic EGFR mutations * HER2 mutation * ALK fusion * ROS1 fusion * RET fusion * NTRK fusion * MET Exon14 skipping mutation * BRAF V600E mutation * Use of any live vaccines within 28 days of C1D1. * Prior chemotherapy in the adjuvant setting or during concurrent radiation therapy for locally advanced disease within 12 months prior to enrollment. If the interval from the last treatment is 12 months or longer, the patient is eligible. * Radiation therapy within 14 days prior to C1D1. * History of major surgery within 14 days prior to C1D1. * Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous, including but not limited to: * History of interstitial lung disease or noninfectious pneumonitis, * Active viral, bacterial or fungal infections requiring parenteral treatment within 14 days of C1D1, * Clinically significant cardiovascular disease, * A condition that may obscure the interpretation of toxicity determination or AEs, * History of prior solid-organ transplantation. * Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (\> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids are not excluded). * HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection. * Evidence of chronic hepatitis B (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection. * History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection. * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy. * Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. * Participants on chronic systemic corticosteroids will be excluded from the study. * Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial. * Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of C1D1. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study, or known hypersensitivity to recombinant proteins, or any excipient contained in the trial formulations. * Pregnant and/or breastfeeding. People of childbearing potential must have a negative pregnancy test within 7 days of study entry.
Study sites (1)
MO
- Washington University School of Medicine · St Louis, MO 63110Giordano Fabricio Cittolin Santos, MD, PhD · Study contact · 314-273-4731 · cgiordano@wustl.eduGiordano Fabricio Cittolin Santos, MD, PhD · Principal investigatorDaniel Morgensztern, MD · Sub-investigatorMaria Q Baggstrom, MD · Sub-investigatorMore trials in St Louis