TG4010 and Nivolumab in Patients With Lung Cancer

Inclusion Criteria: * Histologically confirmed non-squamous NSCLC; patients with adenocarcinoma must have had epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational testing; those with an actionable mutations/rearrangements are excluded * Stage IIIB or IV patients must have progressed after a platinum based chemotherapy; a maximum of 3 previous systemic regimens are allowed (one regimen can be a tyrosine kinase inhibitor); patients with stage I-IIIB NSCLC who have progressed within 6 months of a full dose platinum based regimen as adjuvant therapy or with radiotherapy are eligible; patients who received weekly low dose chemotherapy with radiation only are not eligible * At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) based on RECIST version 1.1 * Performance status (PS) 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Minimum life expectancy of 3 months * Hemoglobin \>= 10.0 g/dL * White blood cells (WBC) \>= 3.0 x 10\^9/L * Neutrophils \>= 1.5 x 10\^9/L * Total lymphocyte count \>= 0.5 x 10\^9/L * Platelet counts \>= 100 x 10\^9/L * Serum alkaline phosphatase =\< 3 x upper limit of normal (ULN) in absence of liver or bone metastases and =\< 5 x ULN in patients with documented bone or liver metastases * Total bilirubin =\< 1.5 x ULN * Serum transaminases (alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\]) =\< 2.5 x ULN in the absence of liver metastases and =\< 5 x ULN in case of liver metastases * Glomerular Filtration Rate \>= 60 mL/min (according to Modification of Diet in Renal Disease \[MDRD\] formula or Cockcroft \& Gault formula) * Serum albumin \>= 30 g/L * Effective contraception during the study period and for 5 months after the last study treatment administration (male and female patient) * Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Patients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least 2 weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of \< 10 mg daily prednisone or equivalent * Prior exposure to cancer immunotherapy including any immune checkpoint inhibitor and/or cancer vaccines * Prior history of other malignancy except: * Basal cell carcinoma of skin * Cervical intra-epithelial neoplasia * Other cancer curatively treated with no evidence of disease for at least 2 years * Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs (e.g. cyclosporine) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to start of the study treatment (day 1 \[D1\] of cycle 1) * Positive serology for human immunodeficiency virus (HIV) or hepatitis C virus (HCV); presence in the serum of the antigen hemoglobin (HBs) * Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g. elevated troponin or creatinine, uncontrolled diabetes) * Patients with major surgery or radiotherapy within 4 weeks prior to the start of the study treatment (i.e. D1 of cycle 1); however, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed one week before treatment start * Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 10 mIU/mL); pregnancy is ruled out by a beta hCG test completed if necessary with an ultrasound * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are: * Women whose sexual orientation precludes intercourse with a male partner * Women whose partners have been sterilized by vasectomy or other means * Using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices \[IUDs\]; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable) * Patient with an organ allograft * Known allergy to eggs, gentamicin, or platinum containing compounds * Hypersensitivity to the active substance or to any of the excipients * Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment (i.e. D1 of cycle 1) * Patient unable or unwilling to comply with the protocol requirements * Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimoto thyroiditis, scleroderma, polyarteritis nodosa, or autoimmune hepatitis * Subject has any peripheral neuropathy \>= National Cancer Institute (NCI) CTCAE grade 2 at enrollment * Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies; any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity * History of any of the following cardiovascular conditions within 12 months of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association * Left ventricular ejection fraction (LVEF) less than the lower limit of normal (LLN) as assessed by echocardiography