Depletion of Myeloid Derived Suppressor Cells to Enhance Anti PD-1 Therapy

Inclusion Criteria

• •1. Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC). Patients should have stage IV disease (AJCC 7th edition), stage IIIb disease that is not amenable to potentially curative treatment (e.g. chemoradiotherapy) or unequivocal progression in a prior irradiated field. Measurable or evaluable disease is required.
• •2. Fresh/ archived tumor tissue available for molecular marker testing is required for entry. A tumor block or at least 5 unstained slides must be available. As an alternative FFPE cell block that is sufficient for histologic analysis is acceptable. If a patient has had PD-L1 status previously determined with and FDA approved assay, they have met this requirement. Tissue is still requested (but not required) for further analysis
• •3. Age \> 18 years.
• •4. ECOG performance status 0 or 1
• •5. Patients must have normal organ and marrow functions as defined below:
• •White blood cells (WBC) \>2,000/mcL; Platelets \>100,000/mcL; Hb ≥9g/dl; Absolute neutrophil count (ANC) \>1,500/mcL; Serum creatinine ≤1.5 x ULN, or
• •Creatinine clearance (CrCl) ≥50 ml/min (if using Cockcroft Gault formula below):
• •Female CrCl= ((140 - age in years)/(72 x serum creatinine in mg/dL)) x weight in kg x 0.85; Male CrCl= ((140 - age in years)/(72 x serum creatinine in mg/dL) x weight in kg x 1.0; AST/SGOT ≤ 3 x ULN
• •Total bilirubin:
• •If no known liver metastasis: total bilirubin ≤ 1.5 x institutional upper limit (ULN) (except, subjects with Gilbert Syndrome who may have total bilirubin \< 3.0 mg/dl; If known metastasis: total bilirubin ≤ 5 ULN
• •6. Negative serum pregnancy test result in Women os Child -bearing Potential (WOCBP)
• •7. Prior therapies:
• •* Patients without activating mutations and gene rearrangements should have received at least one prior chemotherapy regimen. Any number of prior therapies is allowed except for immunotherapy (e.g. anti PD-1, PD-L1, vaccines, CTLA-4 etc.),
• •* Patients with activating mutations with known documented benefit from tyrosine kinase inhibitors should have received and demonstrated progression with that inhibitor (e.g. EGFR del 19 mutation should have been treated with gefitinib, erlotinib or afatanib etc). ALK rearrangements should have been treated with an ALK inhibitor. Patients who have progressed on these agents should be assessed, if appropriate, for resistance mutations susceptible to approved agents and treated with that agent.
• •* No prior gemcitabine treatment
• •8. Ability to understand and willingness to sign a written informed consent and HIPAA consent document
• •5. There must be no requirement for immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• •6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• •7. Uncontrolled inter-current illness that would increase the risk of toxicity or limit compliance with study requirements. This includes but is not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements.
• •8. Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the abnormal immune response that results from HIV disease.
• •9. Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• •10. Patients who have had systemic (IV) cytotoxic chemotherapy or any other investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. If a patient received an oral agent, treatment on study can not commence at least five half-lives of the agent have elapsed.
• •11. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
• •12. Other active malignancy requiring concurrent intervention.
• •13. Subjects with any history of interstitial lung disease.
• •14. Pregnant or breast feeding.