Etirinotecan Pegol (NKTR-102) in NSCLC

Inclusion Criteria: * Histologically or cytologically confirmed metastatic or recurrent NSCLC. Primary or metastatic site may be used for histology. * After failure of 2nd line treatment with up to two prior lines of therapy, one of which may be an oral TKI. * Measurable disease (Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented incontrovertibly either radiographically or pathologically. For clinicians relying on biopsy documentation of recurrence, this must be obtained to confirm persistence at least 90 days following completion of radiation therapy). * Eastern Cooperative Oncology Group (ECOG) performance status is 0-1. * Age at the time of study entry is ≥ 18 years. * Adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9.0 g/dL, and a platelet count ≥ 100,000/μL obtained within 2 weeks prior to enrollment. * Adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal (\[ULN\]), or ≤ 5 × the ULN in the presence of known liver metastases. * Alkaline phosphatase (AP) ≤ 3 x the ULN or ≤ 5 × the ULN in the presence of known liver metastases * Adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the patient's measured or calculated creatinine clearance (CrCl) must be ≥ 50 mL/min. * Resolution of chemotherapy and radiation therapy related toxicities to NCI-CTCAE version 4.0 Grade 1 or lower severity, except for diarrhea (which must be Grade 0 without a supportive antidiarrheal medications) and alopecia (any grade). * Women of childbearing potential and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to enrollment and for the duration of study participation. Protections against pregnancy must be continued for at least 8 months after the last dose of study drug. * Signed informed consent. Exclusion Criteria: * Untreated central nervous system metastases. Patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment. * History of another "active" invasive primary cancer requiring ongoing treatment. * Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent. * Patients who have had chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C), radiotherapy within 14 days, biological therapy within 14 days, hormonal therapy within 7 days, and investigational therapy within 21 days prior to enrollment. * Patients who have had any major surgery within 21 days prior to enrollment. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care (more than 3 days/week) to control diarrhea in the 28 days prior to enrolment. * Administration of the CYP3A4 inducers or inhibitors, as they may induce or inhibit irinotecan or SN38 metabolism within 14 days prior to cycle 1 and throughout study treatment. For a list of these agents, see: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm * Uncontrolled thrombotic or hemorrhagic disorder. * Known human immunodeficiency virus (HIV) positivity. * The patient, if female, is pregnant or lactating. * Previous therapy with a topoisomerase I or II inhibitor. * Known allergy to any of the treatment components.