Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung

Inclusion Criteria: 1. Read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures. 2. Male or female patients with metastatic, histologically- or cytologically-confirmed unresectable Stage IIIB or IV non-small cell lung cancer (NSCLC) of squamous histology (Staging per American Joint Committee on Cancer \[AJCC\], Edition 7). Mixed histology adenosquamous NSCLC will also be permitted. 3. Experienced progression/recurrence of disease during or subsequent to the most recent anti-cancer regimen. 4. Any number of prior lines of systemic therapy may have been received for advanced (recurrent, locally advanced, or metastatic) SCC of the lung, but at least one must have been a platinum-based chemotherapy regimen. Platinum therapy may be given on-label or as part of a clinical trial. 5. Lung cancer confirmed to express gpNMB, as assessed by immunohistochemistry at a central lab (using expression in ≥ 5% of tumor epithelial cells as a cut-off for positivity). This can be tested on archived tissue if available, although preferred tumor specimen is a biopsy after the most recent therapy. 6. Age ≥ 18 years. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1. 8. Measurable disease by RECIST 1.1 criteria. Target lesions selected for tumor measurements should be those where surgical resection or radiation are not indicated or anticipated. 9. Resolution of all toxicities related to prior therapies to ≤ NCI-CTCAE Grade 1 severity, except for alopecia, vitiligo, or endocrinopathies on replacement therapy. 10. Adequate bone marrow function as assessed by absolute neutrophil count (ANC) ≥ 1500/mm3; hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100,000/mm3. 11. Adequate renal function as assessed by serum creatinine ≤ 2.0 mg/dL; or calculated or 24-hour urine creatinine clearance \>40 mL/min. 12. Serum albumin ≥ 3 g/dL. 13. Adequate liver function as assessed by total bilirubin ≤ 1.5x upper limit of normal (ULN), and alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5x ULN (≤ 5.0x ULN in the case of liver metastases). Patients with known Gilbert's syndrome may be enrolled with total bilirubin ≤ 3.0 mg/dL. 14. Both male and female patients of childbearing potential enrolled in this trial must use adequate birth control measures during the course of the trial and for at least one month after discontinuing study drug. 15. Willing to provide blood samples for research purposes. Exclusion Criteria: 1. Received glembatumumab vedotin (CR011-vcMMAE; CDX-011) or other MMAE-containing agents previously. 2. Chemotherapy within 21 days or at least 5 half-lives prior to the planned start of study treatment; radiation outside the thorax within 14 days prior to the planned start of study treatment or thoracic radiation; antibody based therapy or investigational therapy within 28 days prior to the planned start of study treatment. 3. Neuropathy \>NCI-CTCAE Grade 1. 4. Subjects with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin. Compounds of similar composition include Auristatin PHE as an anti-fungal agent, Auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and Symplostatin 1 as an anti-tumor agent. 5. Known brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for 4 weeks. 6. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure related to primary cardiac disease, a history of a serious uncontrollable arrhythmia despite treatment, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry. 7. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary. 8. Subjects on immunosuppressive medications such as azathioprine, mycophenolate mofetil, cyclosporine or require chronic corticosteroid use (defined as ≥ 3 months of prednisone dose equivalent of ≥ 10 mg). 9. The MMAE component of glembatumumab vedotin is primarily metabolized by CYP3A. Patients taking strong CYP3A inhibitor and inducers are excluded in Phase I (the dose escalation portion), to minimize the effect of these modulators on exposure, tolerability and dose selection. 10. History of other malignancy except for adequately treated basal or squamous cell skin cancer, curatively treated in situ disease, or any other cancer from which the patient has been disease-free for ≥ 2 years. 11. Pregnant or breast-feeding women. 12. Subjects must not be on home oxygen therapy (intermittent or continuous). 13. Any underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment hazardous to the patient, or would obscure the interpretation of adverse events.