Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs

Inclusion Criteria

• Patient must be capable, willing, and able to provide written, informed consent.
• ≥ 18 years old.
• Advanced stage NSCLC
• Previously treated with no more than two lines of prior systemic therapy for advanced stage lung cancer.
• Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy may be considered as having received one line of prior therapy
• Maintenance therapy does not count as a separate line of therapy
• Patients must:
• Be scheduled to undergo a standard-of-care resection of tumor tissue as part of treatment plan prior to beginning study therapy. Patients may not have intervening systemic anti-cancer therapy between the time of resection and treatment with nivolumab.
• Have collection of adequate pre-treatment tissue for correlative analysis defined as sufficient material for 1) frozen tissue for DNA/RNA with touch prep/representative slide confirming tumor material present, 2) FFPE material for ICH with touch prep/representative slide confirming tumor material present, and 3) single-cell suspensions with >20 million live cells after tissue digestion but before freezing. Adequacy of collected material will be determined within 5 business days of each collected case.
• Have residual disease following surgical resection that is measurable by RECIST v1.1
• Previously irradiated sites of tumor may be considered measurable if there is radiographic progression at that site subsequent to the time of completing radiation.
• Have a safely biopsiable tumor lesion
• ECOG performance status of 0-1.
• Adequate hematologic, renal, and/or hepatic function (following criteria must be met within 28 days of C1D1:
• WBC ≥ 2,000/ul
• ANC ≥ 1,500/ul
• Hemoglobin ≥ 9.0 g/dl
• Platelet count ≥ 100,000/ul
• Total bilirubin ≤ 1.5 x ULN (unless evidence of Gilbert's syndrome, in which case, direct bilirubin must be ≤ 1.0 x ULN)
• AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly related to metastatic disease involving the liver, in which case AST and ALT must be ≤ 5x ULN)
• Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance of ≥ 40 mL/min calculated using the formula of Cockcroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female
• There is no restriction on the number of prior lines of systemic anti-cancer therapy. For those who have received prior systemic anti-cancer therapy, there must be at least 3 weeks since last systemic therapy.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the start of study drug.
• Effective contraception:
• Women of childbearing potential must agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 23 weeks (5 half-lifes plus 30 days, the duration of an ovulatory cycle) after the last dose of nivolumab, or agree to completely abstain from heterosexual intercourse.
• Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through 31 weeks (5 half-lives plus 90 days, the duration of sperm turnover) after the last dose of study drug, or completely abstain from heterosexual intercourse.

Exclusion Criteria

• Patients who are pregnant or lactating.
• Presence of activating EGFR mutations or ALK re-arrangement,unless previously treated with standard TKI therapy. All patients with adenocarcinoma histology must be tested for EGFR and ALK status.
• History of allergy to study drug components or history of severe hypersensitivity reaction of any monoclonal antibody.
• Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137,