Immunopheresis Alone or in Combination With Paclitaxel or Atezolizumab in Non-small Cell Lung Cancer (NSCLC).

This pilot study will enroll 24 patients with measurable advanced, refractory NSCLC (incurable stage IIIB and stage IV) histologically confirmed as squamous or adenocarcinoma following failure of: * 1st standard line of systemic treatment that included a platinum salt administered in a palliative setting (Arms 1 and 2); or, * 2nd line standard chemotherapy assuming the first line included a platinum salt (Arm 3). Inclusion criteria are to be confirmed within 28 days of the first LW-02 immunopheresis treatment (preferably as proximate to the date of the first treatment as possible): 1. Signed Informed Consent Form 2. Age 18 - 75 years of age 3. Able to comply with the study protocol in the investigator's judgment 4. Histologically or cytologically documented stage IIIb or stage IV squamous or adenocarcinoma NSCLC that has progressed despite 1 line of chemotherapy that included a platinum salt (Arms 1 and 2) or 2 lines of standard chemotherapy assuming the 1st line included a platinum salt (Arm 3). \[Patients with adenocarcinoma must have confirmed negative status of EGFR gene mutation and ALK fusion gene and ROS1.\] * Patients who discontinued previous treatments (first- or second-line) due to intolerance are also eligible. * Staging must be according to the UICC/AJCC system, 7th edition (Detterbeck et al. 2009) * Pathological characterization may be conducted on tumor specimens from earlier stage disease, but the tumor samples must have been sufficient to confirm squamous or adenocarcinoma histologically * Combined radiation/chemotherapy treatment (chemoradiation) counts as one prior chemotherapy regimen if \< 6 months have elapsed between the last dose and the date of recurrence * Adjuvant/neoadjuvant chemotherapy is not counted as a line of treatment except for cases where the relapse is diagnosed \< 6 months from the end of adjuvant/neoadjuvant chemotherapy that included a platinum salt. * Debulking surgery and anticancer agents used for pleurodesis are not counted as lines of therapy 5. Must be able to provide archival pathological material from primary or metastatic site (formalin-fixed paraffin embedded \[FPPE\] tissue block) for central NSCLC confirmation and verification of NSCLC subtype and tmTNF expression 6. Body mass ≥ 35 kg 7. Life expectancy of at least 3 months with malignancy; expected to live for one year without malignancy. 8. Adequate organ function: 1. Hemoglobin ≥ 9.5g/dL (may be achieved with transfusion support) 2. Absolute Neutrophil Count (ANC) ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment) 3. Platelets (PTL) ≥ 100 × 109/L 4. AST/ALT ≤2.5×ULN (patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN; patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN) 5. Serum creatinine (S-Cr) ≤ 1.2 ULN 6. Albumin ≥ LLN 7. Bilirubin ≤ 1.5 ULN 8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagulation agents. 9. Patients should not be receiving therapeutic anticoagulation. Prophylactic low doses of ASA are acceptable. 10. Serum calcium level within normal range. 9. The last dose of prior systemic anticancer therapy must have been administered * 14 days prior to study treatment initiation assuming all substantial chemotherapy toxicities recovered satisfactorily. 10. Having not used antibiotics in the last month prior the start of the screening or, at least, prior to obtaining a baseline microbiome sample. 11. Measurable disease, as defined by RECIST v1.1 12. Patients with asymptomatic CNS metastases (treated or untreated), as determined by CT or MRI evaluation during screening and prior radiographic evaluation, are eligible if do not require corticosteroids dose adjustments due to in the last 4 weeks. 13\. ECOG performance status 0, 1 or 2. 14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use double barrier contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 5 months after the last treatment. 15\. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia. Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: 1. Symptomatic CNS metastases 2. Leptomeningeal disease 3. Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures 4. Previous use of paclitaxel (not applicable for patients enrolled in Arm 3). 5. Pregnant or lactating or intending to become pregnant during the study or for at least 5 months after the least study treatment. Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study treatment 6. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) 7. Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina 8. Patients with known coronary artery disease or left ventricular ejection fraction \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate 9. Patient with known persistent, uncontrolled hypotension 10. Significant renal disorder requiring dialysis or indication for renal transplant 11. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation 12. Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis 13. Fever, or any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection 14. Other serious diseases (e.g., life expectancy less than 3 months) including active second malignancy except for basal cell carcinoma or cervical carcinoma in situ 15. Active infection 16. Patients in whom vascular access is not considered achievable 17. Use of any standard high dose or low dose chemotherapy or immunosuppressive therapies and or standard radiation therapy concurrently as well anticipated need for any of the former during the study 18. Body mass index (BMI) ≥ 35 kg/m2 19. Any condition that the patient's physician determines to be detrimental to the patient participating in this study; including any clinically important abnormal clinical laboratory values or concurrent medical events 20. Inability to understand the local language affecting the use of the patient QOL instruments. 21. Need for regular treatment with an angiotensin converting enzyme (ACE) inhibitor during the study; patients should discontinue treatment at least 14 days prior to the first LW-02 column immunopheresis treatment. Additional exclusions for patients to be treated in Arm 1 (with atezolizumab): 1. Previous use of atezolizumab. 2. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 3. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation 4. History of autoimmune disease is allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks, with the exception of: 1. Patients taking concurrent abatacept or belatacept treatment (prior therapy must have been withdrawn for \> 8 weeks) 2. Patients with a history of serious or life threatening immune-related events 3. No more than 1 concomitant autoimmune disease at the time of study entry is allowed unless one of them is: i. Autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone ii. Controlled Type I diabetes mellitus on a stable dose of insulin regimen iii. A medical history of such entities as atopic disease or childhood arthralgia, where the clinical suspicion of autoimmune disease is low. In addition, transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent are not excluded (eg, acute Lyme arthritis) iv. Vitiligo. 5. Prior allogeneic stem cell or solid organ transplantation 6. History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted 7. Active tuberculosis a. In patients who have a potentially high likelihood of latent tuberculosis (e.g., recent contact with an infectious carrier, residence in a locale with high TB burden), absence of Mycobacterium tuberculosis infection must be confirmed before enrollment according to local practice standards 8. Administration of a live, attenuated vaccine within 4 weeks prior to study treatment initiation 1. Influenza vaccination should be given during influenza season only (e.g., approximately October to March in the Northern Hemisphere). 2. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to study treatment initiation or at any time during the study. 9. Prior treatment with CD137 agonists or immune checkpoint blockade therapies other than anti-PD-1 therapy, including anti-PD-L1 therapeutic antibodies 10. Treatment with systemic immunostimulatory agents (including, but not limited to, interferons or interleukin 2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to initiation of study treatment a. Prior cancer vaccines and cellular immunotherapy are permitted 11. Specifically for patients without autoimmune disease: treatment with systemic corticosteroids or other systemic immunosuppressive medications including, but not limited to: prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents within 2 weeks prior to study treatment initiation, or anticipated requirement for systemic immunosuppressive medications during the trial 1. For patients with CNS metastases and lung cancer related dyspnea, use of prednisone at a stable dose (or dose equivalent) of ≤ 20 mg/day is acceptable. 2. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (eg, fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids for cutaneous diseases are allowed.