EOpredict-Lung is a clinical study in subjects with histologically or cytologically confirmed, early stage or locally advanced non-small cell lung cancer (NSCLC) eligible for curative resection. This study will determine the feasibility of two cycles of preoperative immunotherapy with nivolumab or as combination nivolumab plus relatlimab.
- Conditions
- non-small cell lung cancer (NSCLC) of clinical stages IB, II and selected stage III AMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002478-29-NL
- Lead Sponsor
- niversity Hospital Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
•Patients with histologically (core biopsy) or cytologically (e.g. bronchoscopy-guided biopsy) confirmed non-small cell lung cancer (NSCLC) eligible for anatomic resection, with the following specifications:
oClinical stages I B, II and selected stage III A (T3 N1, T4 with satellite nodule in the same lung N0/N1, selected T1a-T2b N2 cases considered suitable for primary surgical approach by the multidisciplinary tumor board) according to UICC 8th edition
•Males and females, ages ? 18 years, inclusive
oWomen of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study treatment.
oWomen of childbearing potential (WOCBP) must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment with study medication plus 5 half-lives of study treatment plus 30 days (duration of ovulatory cycle) post treatment completion for a total of 165 days (approximately 24 weeks) (Appendix IV). This applies to both treatment arms, nivolumab monotherapy and nivolumab/relatlimab combination therapy.
oMales who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception and fetal protection (Appendix IV) for the duration of treatment with study medication plus 5 half-lives of the study treatment plus 90 days (duration of sperm turnover) for a total of 225 days (approximately 33 weeks) post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. This applies to both treatment arms, nivolumab monotherapy and nivolumab/relatlimab combination therapy.
•ECOG = 1
•Exclusion of extensive mediastinal lymph node metastases (multilevel N2, N3) by PET/CT and/or invasive mediastinal lymph node staging by EBUS-TBNA and/or staging mediastinoscopy as indicated by current guidelines.
•Exclusion of distant metastases by standard of care imaging studies, which include but are not limited to PET/CT or PET/MRI, or CT or MRI of thorax, abdomen, pelvis, and bone scan. Asymptomatic brain metastases will be excluded by MRI or contrast-enhanced CT as indicated by current guidelines.
•Measurable target tumor prior to immunotherapy using standard imaging techniques.
•Sufficient pulmonary function to undergo curative lung cancer surgery, ppFEV1>30%, ppDLCO>30%, ppVO2max ? 10 ml/min/kg (if CPET was mandated per local guidelines)
•Adequate hematological, hepatic and renal function parameters:
•Sufficient cardiac left ventricular defined as LVEF = 50% documented either by echocardiography or MUGA (echocardiography preferred test, MUGA not used in German site) within 6 months before first administration of study drug
•Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
•Active or history of autoimmune disease or immune deficiency
•Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
•Subjects who have undergone organ transplant or allogeneic stem cell transplantation.
•ppFEV1<30%, ppDLCO<30%, ppVO2max < 10 ml/min/kg (if CPET was mandated per local guidelines)
•Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
oMyocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
oUncontrolled angina within the 3 months prior to consent
oAny history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
oQTc prolongation > 480 msec
oPulmonary hypertension (sPAP >35 mmHg)
•History of other clinically significant cardiovascular disease
•Cardiovascular disease-related requirement for daily supplemental oxygen
•History of two or more myocardial infarctions or two or more coronary revascularization procedures
•Subjects with history of myocarditis, regardless of etiology
•Troponin T (TnT) or I (TnI) > 2 × institutional upper limit of normal (ULN). Subjects with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are within ULN. If TnT or TnI levels are >1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the coordinating investigator or designee. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the coordinating investigator or designee.
•Patients with active neurological disease should be excluded.
•Active malignancy or a prior malignancy within the past 3 years.
•Known history of positive test for human immunodeficiency virus (HIV-1 and HIV-2) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV-1 and HIV-2 must be performed at screening.
•Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV RNA negative).
•Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
•Receipt of live attenuated vaccine within 30 days prior to the first dose of study medication
•Peripheral polyneuropathy NCI CTCAE Grade = 2
•History of gastric perforation or fistulae in past 6 months
•Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
•The patient has undergone major surgery within 28 days prior to enrollment except staging mediastinoscopy, diagnostic VATS or implantation of a venous port-system.
•Any other concurrent preoperative antineoplastic treatment including irradiation
•Pregnant women
•Breastfeeding women
•Insufficient cardiac left ventricular function defined as LVEF<50%
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method