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Neoadjuvant nivolumab combination treatment in resectable non-small cell lung cancer patients: Defining optimal combinations and determinants of immunological response (NEOpredict-Lung)

Phase 2
Active, not recruiting
Conditions
non-small cell lung cancer (NSCLC) of clinical stages IB, II and selected stage III A
Registration Number
2024-513074-22-00
Lead Sponsor
Universitaetsklinikum Essen AöR, Universitaetsklinikum Essen AöR
Brief Summary

The primary objective of this study is to determine the feasibility of four weeks of preoperative immunotherapy with nivolumab, nivolumab plus relatlimab at different dosis in patients with early stage or locally advanced non-small cell lung cancer eligible for curative resection.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruitment ended
Sex
Not specified
Target Recruitment
90
Inclusion Criteria

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: o Clinical 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

Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Males and females, ages ≥ 18 years, inclusive o Women 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. o Women 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 months after the last dose of the study drug.

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

Exclusion Criteria

Active or history of autoimmune disease or immune deficiency

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. Patients with the following conditions are not excluded from participation:[..]

Known history of positive test for human immunodeficiency virus (HIV-1 and HIV-2) or known acquired immunodeficiency syndrome (AIDS). [..]

Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen positive, or hepatitis C antibody [..]

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

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.

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% by echocardiography (outside Germany: or MUGA scan) within 6 months before first administration of study drug

A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent

Subjects with history of severe toxicity or life-threatening toxicity (grade 3 or 4) related to prior immune therapy (e.g.[..] except those that are unlikely to re-occur with standard countermeasures [..]

Subjects with history of severe or life-threatining (grade 3 or 4) infusion-related reactions to prior immune therapy

Prior treatment with LAG-3 targeting agent

Participation in another interventional clinical study within the last 3 months prior to inclusion or simultaneous participation in other clinical studies

Subjects who have undergone organ transplant or allogeneic stem cell transplantation

Previous treatment with nivolumab or relatlimab

Previous immunotherapy for lung cancer

Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject’s safety

Any contraindications against nivolumab or relatlimab

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: [..]

History of other clinically significant cardiovascular disease (i.e.[..])

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Primary variable is the number of patients undergoing curatively intended surgery of non-small cell lung cancer within 43 days of initiation of study therapy.

Primary variable is the number of patients undergoing curatively intended surgery of non-small cell lung cancer within 43 days of initiation of study therapy.

Secondary Outcome Measures
NameTimeMethod
Objective response rate (RECIST 1.1)

Objective response rate (RECIST 1.1)

Pathological response rate per ypTNM classification and per IASLC recommendations [..]

Pathological response rate per ypTNM classification and per IASLC recommendations [..]

R0 resection rate

R0 resection rate

Disease-free survival rate at 12 months per RECIST 1.1

Disease-free survival rate at 12 months per RECIST 1.1

Overall survival rate at 12 months

Overall survival rate at 12 months

Safety and tolerability of preoperative immunotherapy

Safety and tolerability of preoperative immunotherapy

Morbidity and mortality within 90 days of curative surgery

Morbidity and mortality within 90 days of curative surgery

Translational parameters [..]

Translational parameters [..]

Trial Locations

Locations (4)

Jessa Ziekenhuis

🇧🇪

Hasselt, Belgium

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

🇳🇱

Amsterdam, Netherlands

Thoraxklinik Heidelberg gGmbH

🇩🇪

Heidelberg, Germany

Universitaetsklinikum Essen AöR

🇩🇪

Essen, Germany

Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Kristof Cuppens
Site contact
0032472565987
kristof.cuppens@jessazh.be

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