Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node or Other High Risk Features

The goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with select N3 lymph node involvement or other high-risk subsets in which there is no consensus on resectability. The main question it aims to answer is whether patients with stage 3 NSCLC with involvement of lymph nodes can undergo surgery to remove the cancer after receiving treatment with chemotherapy + immunotherapy. Participants will receive FDA-approved chemotherapy called platinum-doublet chemotherapy together with an immunotherapy drug targeting the immune marker PD-1 called cemiplimab. Patients will receive a 3 drug combination for 4 total treatments given every 3 weeks before surgery. After surgery, patients will have the option to undergo radiation therapy if it is recommended by their treatment team. After this, they will receive cemiplimab every 3 weeks for one year.

Inclusion Criteria: 1. Age ≥ 18 years at time of signing the informed consent form (ICF). 2. Histologically or cytologically confirmed stage 3 Non-Small Cell Lung Cancer (NSCLC) as assessed per the 8th American Joint Committee on Cancer (AJCC) that meets one of the below criteria: 1. Pathologically-confirmed contralateral mediastinal or ipsilateral supraclavicular (N3) lymph node involvement. Primary tumor and involved lymph nodes should otherwise be deemed appropriate for resection/removal with curative intent as assessed by the treating surgeon prior to study enrollment. 2. Pathologically-confirmed T4N2 NSCLC. 3. Pathologically-confirmed T4inv with any N. 4. Pathologically-confirmed T3invN2. 5. Pathologically-confirmed Pancoast T3 or T4 with N2 involvement. 6. Any T-stage with bulky N2 lymph node involvement defined by lymph node short axis ≥ 2.5cm. 3. Absence of major associated pathologies and co-morbidities that elevate surgery risk to a prohibitive level, as assessed by treating surgeon prior to study enrollment. 4. Pulmonary function capacity capable of tolerating the lung resection proposed by the treating surgeon. 5. EGFR, ALK, wild-type assessed via any CLIA-certified tissue testing platform. Documentation of EGFR and ALK status is not required for pure squamous NSCLC histology. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 7. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 21 days prior to initiation of study treatment: 1. Absolute Neutrophil count (ANC) ≥ 1.0 x 10\^9/L (1000/uL) without granulocyte colony-stimulating factor support 2. Platelet count ≥ 100 x 10\^9/L (100,000/uL) without transfusion 3. Hemoglobin ≥ 90 g/L (9.0 g/dL) (Patients may be transfused to meet this criterion.) 4. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \