Atezolizumab Immunotherapy in Patients With Advanced NSCLC

Inclusion Criteria

• Newly diagnosed stage IIIA/B NSCLC, PS 0-1
• No active autoimmune disease or uncontrolled infection, normal bone marrow, renal, hepatic function, FEV1 > 1.2L, no significant underlying heart or lung disease
• Pathologically proven diagnosis of NSCLC
• Measurable Stage IIIA or IIIB disease
• Tissue available for PD-L1 testing and for correlative science testing
• Patients must be considered unresectable or inoperable. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
• No prior chemotherapy or radiation for this lung cancer.
• Prior curative-intent surgery at least 3 months prior to the nodal recurrence.
• Stage III A or B disease with minimum diagnostic evaluation within 6 weeks to include:
• History/physical examination
• Contrast enhanced CT of the chest and upper abdomen
• MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated)
• PET/CT
• If pleural fluid is visible on CT scan thoracentesis to exclude malignancy should be obtained. Patients with effusions that are too small to tap are eligible.
• Patients must be at least 4 weeks from major surgery and must be fully recovered
• Age greater than or equal to 18 years.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks or at least 4 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression.
• If an archived tumor block exists, then either the block or at least 4 unstained slides from the block should be submitted. Tumor tissue should be of good quality based on total and viable tumor content, i.e. at least 50 viable tumor cells and intact tissue architecture. Fine needle aspiration, brushing,and lavage samples are not acceptable. If the block is tissue from a core-needle biopsy, then the block should contain tissue from at least three cores to be sufficient for evaluation.
• Patients who do not have existing (archived) tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum of three cores) or excisional, or forceps biopsies for endobronchial or nodal lesions. The tissue should be fixed in formalin and embedded on site and sent as a block.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
• ANC ≥ 1500 cells/µL
• WBC counts > 2500/µL
• Lymphocyte count ≥ 300/µL
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 10.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:
• Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
• AST and ALT ≤ 3.0 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
• (140 - age) x (weight in kg) x (0.85 if female)/ 72 x (serum creatinine in mg/dL)
• Measurable disease per RECIST v1.1 (see Appendix 3)
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [ 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)
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• 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 onl