A Study of Nivolumab +/- Nab-paclitaxel in Non-small Cell Lung Cancer
Condition: Non-Small-Cell Lung Cancer Metastatic; Non-Small Cell Carcinoma of Lung, TNM Stage 4; Nonsmall Cell Lung Cancer; Non Small Cell Lung Cancer Recurrent
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Nivolumab; nab-paclitaxel
Intervention description: Arm A: Nivolumab 240 mg via intravenous infusion (IV) over 30 minutes day 1 of each 14 day cycle until disease progression or not tolerated.
Arm B: Nivolumab 360 mg via intravenous infusion (IV) over 30 minutes day 1 of every 21 day treatment cycle until progression or not tolerated.; Patients in arm B receive nab-paclitaxel at a dose of 100 mg/m2 over intravenous infusion on Days 1 and 8 of each 21 day cycle.
Intervention MeSH terms: Paclitaxel; Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The optimal prioritization of second-line chemotherapy and immune therapy based on
      demographic or biomarker data is an area of ongoing investigation. The hypothesis of this
      study is that there may be an additive or synergistic antitumor effect of combined
      chemotherapy and nivolumab in the second-line treatment of NSCLC as an important concept to
      test in a clinical trial. Previously treated NSCLC remains a setting of unmet clinical need
      despite recent clinical research progress. Early progression for a subset of NSCLC patients
      receiving nivolumab is a specific area of clinical need.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically confirmed, Stage IV non-small cell lung cancer (per
             the Union Internationale contre le Cancer/American Join Committee on Cancer staging
             system, 7th edition) or recurrent incurable non-small cell lung cancer that has
             progressed after first-line chemotherapy.

          2. Prior Therapy: Platinum doublet chemotherapy for current diagnosis of advanced lung
             cancer. Only one prior line of chemotherapy for advanced lung cancer allowed. Adjuvant
             chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy given for early stage
             lung cancer at least 6 months prior to diagnosis of recurrent/metastatic disease is
             not counted as a line of therapy for advanced lung cancer. Patients who received
             platinum doublet therapy with or without radiotherapy as part of treatment for early
             stage non-small cell lung cancer less than 6 months after developing stage 4 or
             recurrent incurable disease will be considered study eligible by the criterion of
             having received one line of chemotherapy for non-small cell lung cancer.

          3. EGFR, ALK and ROS biomarker positive tumors are eligible as long as the patient has
             received at least one standard oral, molecular inhibitor therapy in addition to
             standard platinum doublet chemotherapy. More than one molecular inhibitor is allowed
             such as a first generation EGFR inhibitor followed by a next generation EGFR inhibitor
             when T790 mutation develops. Prior molecular therapy for biomarker positive tumors
             such as (but not limited to) MET, RET and BRAF allowed but not required.

          4. Prior chemotherapy must have been completed 21 days prior to initiation of protocol
             therapy and all toxicities must < grade 2.

          5. Patients must have < Grade 2 or pre-existing neuropathy (per CTCAE).

          6. Palliative radiation must have been completed 2 weeks prior to the initiation of study
             therapy.

          7. All patients must have measurable disease. Measurable disease is defined as at least
             one lesion that can be accurately measured in at least one dimension (longest diameter
             to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT
             scan.

          8. ECOG Performance Status: 0-1

          9. Second malignancy: No "currently active" second malignancy other than non-melanoma
             skin cancers.

         10. Brain metastases: brain metastases must have been treated at least 2 weeks prior to
             enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be
             receiving a supra-physiologic dose of steroids (> 10 mg prednisone daily or
             equivalent).

         11. Non-pregnant and non-nursing. The effect of nab-paclitaxel and nivolumab on the fetus
             is unknown.

         12. Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 6 months after the last dose of study medication. Patients of
             childbearing potential are those who have not been surgically sterilized or have not
             been free of menses > 1 year.

         13. Male patients must agree to use an adequate method of contraception starting with the
             first dose of study therapy through 7 months after the last dose of study therapy.

         14. Age ≥18 years.

         15. Required Initial Laboratory Values:

             Leukocytes ≥2000/ µl Hemoglobin >9.0 g/dL Platelets ≥100,000/ µl ANC ≥1,500/mcL

             Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the
             Cockcroft-Gault formula below):

             Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in
             mg/dL

             Male CrCl = (140 - age in years) x weight in kg x 1.00

             Total Bilirubin <1.5 mg/dl (except for subjects with Gilbert Syndrome, who can have
             total bilirubin < 3.0 mg/dl) SGOT (AST) <2.5 x ULN ALP <2.5 x ULN in absence of liver
             metastases (<5 x ULN if liver metastases present PTT <1.5 x ULN

         16. An archival tumor sample from either a prior core needle biopsy or surgical specimen
             must be available to be submitted for correlative studies as an eligibility
             requirement prior to registration. The sample must be shipped within 6 weeks of
             enrollment. Participants without an available archival tumor sample are considered
             ineligible.

        Exclusion Criteria:

          1. Prior nab-paclitaxel chemotherapy excluded.

          2. Prior immune therapy for NSCLC excluded. Patients should be excluded if they have had
             prior treatment with an anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4 antibody, or
             any other antibody or drug specifically targeting T-cell costimulation or immune
             checkpoint pathways.

          3. Patients will be excluded if they have an active, known or suspected autoimmune
             disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger.

          4. Patients will be excluded if they have a condition requiring systemic treatment with
             either corticosteroids (>10mg/day prednisone equivalents) or other immunosuppressive
             medications within 14 days of study drug administration. Inhaled or topical steroids
             and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the
             absence or active autoimmune disease.

          5. Patients should be excluded if they test positive for hepatitis B virus surface
             antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
             acute or chronic infection.

          6. Patients should be excluded if they have known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

          7. Allergies and Adverse Drug Reaction: History of allergy to study drug components