Evaluating the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer (NSCLC)

Exclusion Criteria

• •Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
• •* Hormone-replacement therapy or oral contraceptives.
• •* Herbal therapy greater than 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1).
• •* Hormonal therapy for prostate cancer or breast cancer provided criteria in 3.2.21 are met.
• •* Palliative radiotherapy (e.g., treatment of known bony metastases) allowed, provided it does not interfere with the assessment of tumor target lesions (e.g. the lesion being irradiated is not the only site of disease, because that would render the patient not evaluable for response by tumor assessments according to RECIST v1.1).
• •Adverse events from prior anticancer therapy that have not resolved to Grade equal to/less than1 except for alopecia.
• •History of grade 4 immune-related adverse events requiring treatment with prednisone or history of grade 3 immune-related adverse events requiring prednisone \>10 mg/kg for \>12 weeks.
• •Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed).
• •Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
• •Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma.
• •Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
• •* Evaluable or measurable disease outside the CNS.
• •* No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm).
• •* No history of intracranial hemorrhage or spinal cord hemorrhage.
• •* No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
• •* No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1.
• •Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
• •* Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
• •* No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1.
• •* Screening CNS radiographic study equal to/greater than 4 weeks from completion of radiotherapy and equal to/greater than 2 weeks from discontinuation of corticosteroids.
• •Patients who are pregnant, are lactation, or breastfeeding.
• •Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
• •Inability to comply with study and follow-up procedures.
• •History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
• •* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
• •* Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
• •* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• •* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations.
• •* Rash must cover less than 10% of body surface area (BSA).
• •* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%).
• •* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
• •History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• •History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection.
• •* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible.
• •* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• •Active tuberculosis.
• •Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• •Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
• •Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• •Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
• •Administration of a live, attenuated vaccine within 4 weeks before enrollment or anticipation that such a live attenuated vaccine will be required during the study or for 5 months after the last dose of Atezolizumab. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to enrollment, at any time during the study, or for 5 months after the last dose of Atezolizumab.
• •Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score equal to/less than 6, and prostate-specific antigen equal to/less than10 mg/mL, etc.).
• •Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half lives of the investigational product, whichever is longer).
• •Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Cycle 1, Day 1.
• •* Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
• •* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• •Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.