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

Inclusion Criteria:

• Patients with histologically confirmed non-small cell lung cancer (NSCLC) eligible for anatomic resection (Clinical stages I B, II and selected stage III A)
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Sufficient pulmonary function to undergo curative lung cancer surgery
• Adequate hematological, hepatic and renal function parameters:
• Sufficient cardiac left ventricular defined as left ventricular ejection fraction (LVEF) ≥ 50% documented either by echocardiography or multigated acquisition scan (MUGA)
• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Exclusion Criteria:

• 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
• Uncontrolled or significant cardiovascular disease
• Patients with active neurological disease
• Active malignancy or a prior malignancy within the past 3 years
• 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 Video Assisted Thoracoscopic Surgery (VATS) or implantation of a venous port-system.
• Any other concurrent preoperative antineoplastic treatment including irradiation
• Pregnant/Breastfeeding women
• Subjects with history of severe toxicity or life-threatening toxicity (grade 3 or 4) related to prior immune therapy
• Prior treatment with Lymphocyte-activation gene 3 (LAG-3) targeting Agent
• Previous treatment with Nivolumab or Relatlimab