Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer

Inclusion Criteria

• Cooperation and willingness to complete all aspects of the study
• Signed and dated written informed consent must be given prior to study inclusion
• Histological or cytological confirmed NSCLC
• Clinical stage II-IIIA according to the TNM classification, 7th edition:

stage IIIa: T1/T2 N2 (IIIa1-3 Robinson classification)

• Adequate disease staging by PET/CT and brain MRI
• At least 1 measurable lesion according to RECIST 1.1
• Age ≥ 18 years
• ECOG performance status 0 - 1
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Adequate bone marrow function, liver and renal function:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Thrombocytes ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
• INR 2.5 mg/dL
• 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 subject with creatinine levels > 1.5 X institutional ULN
• Adequate lung and cardiac function for intended lung resection according to German S3 guideline

Exclusion Criteria

• Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
• Participation in a clinical trial within the last 30 days prior to study treatment
• History of allogeneic tissue/solid organ transplant
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Evidence of interstitial lung disease.
• cT4 tumor
• Symptomatic acute cardiovascular or cerebrovascular disease
• Known active HBV, HCV or HIV infection
• Has any other active infection requiring systemic therapy.
• Patients with active tuberculosis
• Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1
• Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy in history.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months 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 Sjorgen's syndrome will not be excluded from the study.
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