Carboplatin and Nab-paclitaxel with Pembrolizumab in Treating Patients with Stage IIIB or IV Non-small Cell Lung Cancer That is Unable To Be Removed with Surgery

Inclusion Criteria

• Subjects must be willing and able to provide written informed consent for the trial and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of protected health information * NOTE: HIPPA authorization may be included in the informed consent or obtained separately
• Individuals with stage IIIB or IV, unresectable non-small cell lung cancer (NSCLC) who have not received prior chemotherapy for stage IIIB or IV disease, and who are not candidates for curative surgery or radiation therapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
• Prior to registration, all subjects must have adequate archival tissue available prior (unstained slides are to be submitted as outlined in the study procedures manual); if no acceptable archival tissue is available, the subjects must be willing to consent to providing a mandatory pre-treatment core biopsy for research; phase II subjects must be willing to consent to providing a mandatory post-treatment core biopsy for research; fine needle aspiration and cytology samples will not be acceptable
• Women are eligible to participate if they are of non-childbearing potential or have documentation of a negative pregnancy test (serum or urine beta-hCG [human chorionic gonadotropin]) within 3 days of registration; sexually active pre-menopausal women of childbearing potential must agree to use adequate, highly effective contraceptive measures, starting with the first dose of study drug and for 120 days after the last dose of last study drug; effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable, or injectable contraceptives plus one barrier method; or (c) 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >= 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of last study drug

Exclusion Criteria

• Individuals with the presence of symptomatic central nervous system (CNS) metastases requiring radiation treatment, surgery, or ongoing use of corticosteroids
• Untreated or brain metastasis causing any symptoms, such as neurologic deficits or headache; individuals with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline and whole brain radiation or stereotactic radiosurgery completed over 4 weeks prior to registration), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment
• History of solid organ or stem cell transplant requiring immunosuppressive medications
• Any prior adjuvant cytotoxic chemotherapy within 12 months of registration; subjects who received chemotherapy for earlier stage disease more than 12 months prior to study registration are eligible for this trial
• Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Any radiotherapy within 2 weeks of registration
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• History of other invasive malignancy that is currently active and/or has been treated within 12 months of registration; (notable exceptions include: basal cell carcinoma, squamous cell carcinoma of the skin, localized prostate cancer, in situ carcinomas of the cervix and breast, and superficial bladder cancers [non-muscle-invasive])
• Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis
• Has active, non-infectious pneumonitis
• Pre-existing peripheral neuropathy that is >= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 criteria
• Known significant liver disease including viral, alcoholic, active hepatitis B or C, and/or cirrhosis
• Bilirubin >= 1.5 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 2.5 x the upper limit of normal (ULN)
• Alkaline phosphatase > 2.5 x the ULN, there is no upper limit if bone metastasis is present in the absence of liver metastasis
• Creatinine > 1.5 mg/dL
• Absolute neutrophil count (ANC) < 1.5 x 10^9/L
• Hemoglobin < 9.0 g/dL; patients may not be transfused to meet enrollment criteria
• Platelets < 100 x 10^9/L
• International normalized ratio (INR) of prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Has received a live vaccine within 30 days prior to the first dose of study drug
• Known activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab