Nivolumab and Tumor Infiltrating Lymphocytes (TIL) in Advanced Non-Small Cell Lung Cancer

Inclusion Criteria

• Age >18 years
• Able to understand and give written informed consent
• Confirmed or suspected diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC). For suspected NSCLC, diagnosis must be histologically or cytologically confirmed prior to start of nivolumab treatment. Neuroendocrine cancers, or mixed neuroendocrine features in >10% of tumor cells, are excluded.
• Tumor deemed accessible by metastasectomy (TIL harvest) which expects to yield >1.5 cm^3 of resectable tumor amount.
• Measurable disease, even after resection of applicable lesion for TIL harvest. Defined as ≥1 lesion that is ≥10 mm in one dimension by CT scan, MRI, or calipers on clinical exam.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Expected survival > 6 months
• Patients with activating Epidermal Growth Factor Receptor (EGFR) mutation or Anaplastic Lymphoma Kinase (ALK) rearrangement which is expected to be responsive to available tyrosine kinase inhibitor therapy, must have been previously treated with an applicable tyrosine kinase inhibitor.
• Adequate normal organ and marrow function in an assessment performed within 7 days (+ 3 day window) of enrollment, defined as: Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (> 1000 per mm^3); Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3); Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) ≤ 1.5x the institutional upper limit of normal (ULN), (This will not apply to patients with confirmed Factor XII deficiency.); Serum bilirubin ≤ 1.5x the institutional ULN, or ≤ 3x ULN if confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology); Aspartate Aminotransferase (AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN; Serum creatinine of ≤ 1.5x institutional ULN; Albumin ≥ 2.5 g/dl.
• Positive screening Epstein Barr Virus (EBV) antibody titer on screening test.
• Cardiac stress test within past 6 months without evidence of reversible ischemia.
• Cardiac echocardiogram, stress test, or Multigated Acquisition Scan (MUGA) within past 6 months with demonstrated left ventricular ejection fraction (LVEF) > 50%
• Pulmonary function tests within past 6 months showing Diffusion Lung Capacity for Carbon Monoxide (DLCO) >50% of predicted. Adjusted DLCO based on hemoglobin concentration should be used, if available.

Exclusion Criteria

• More than 5 lines of prior systemic therapy in the preceding 3 years.
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including but not limited to: nivolumab, atezolizumab, pembrolizumab, or durvalumab.
• Current or prior use of any immunosuppressive medications, such as corticosteroids, within 14 days before enrollment. a.) Oral hydrocortisone, only for the purposes of a documented and confirmed adrenal insufficiency diagnosis, is permitted if ≤ 25 mg daily total dose. b.) Inhaled, intranasal, or topical corticosteroids are permitted.
• Patients with untreated brain metastases. Treated brain metastases with radiation or surgery are allowed if: ≤ 3 cm in size AND ≤ 4 in number AND there is no evidence of progressive disease, on brain imaging ≥ 28 days after last day of central nervous system (CNS) treatment.
• History of leptomeningeal metastases.
• Current or prior use of anticancer therapy before TIL collection: a.) Chemotherapy within the past 4 weeks; b.) Tyrosine kinase inhibitor (TKI) within the past 1 week; c.) Investigational therapy within the past 4 weeks or 4 half-lives, whichever is shorter.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than stable atrial fibrillation) and significant carotid artery stenosis.
• Known to be HIV positive, hepatitis B or C positive, or both Rapid P