Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients

Inclusion Criteria:

• REGISTRATION STEP 1: Participants must have pathologic (cytological or histological) proof of non-small cell lung cancer (NSCLC)

• REGISTRATION STEP 1: Participants must have stage III NSCLC with Zubrod performance status of 2 or stage II NSCLC with Zubrod performance status of 0-2

• REGISTRATION STEP 1: Participants must not be candidates for surgical resection in the opinion of the treating investigator. Participants whose disease was previously resected must have experienced local or regional recurrence at least 12 months after resection

• REGISTRATION STEP 1: Participants must not be candidates for concurrent chemoradiation in the opinion of the treating investigator

• REGISTRATION STEP 1: Participants must have measurable or non-measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to Registration Step 1. Non-measurable disease must be assessed within 42 days prior to Step 1 registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)

• REGISTRATION STEP 1: Participants must have an MRI or CT scan of the brain with contrast within 28 days prior to Registration Step 1

• REGISTRATION STEP 1: Participants' disease must fit within the radiation constraints in the opinion of a local radiation oncologist

• REGISTRATION STEP 1: Participants may have received prior treatment for their lung cancer, including surgery, chemotherapy, targeted agents, and/or radiation treatment. At least 12 months must have elapsed since last treatment

• REGISTRATION STEP 1: Participants may have had prior radiation therapy as long as the irradiated area does not overlap with the radiation field targeted for this study

• REGISTRATION STEP 1: Participants must have recovered from any adverse effects of prior major surgery to the satisfaction of the treating physician. Biopsies and central IV access placement are not considered major surgery

• REGISTRATION STEP 1: Absolute neutrophil count (ANC) >= 1500/mcl (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Platelet count >= 100,000/mcl (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Hemoglobin >= 9 grams/dL (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Serum creatinine =< 1.5 x IULN OR measured or calculated creatinine clearance >= 40 mL/min (obtained within 28 days prior to Registration Step 1)

• REGISTRATION STEP 1: Participants must have percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) of at least 40% documented within 90 days prior to Registration Step 1

• REGISTRATION STEP 1: Patient must not have had a prior history of interstitial lung disease or > grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version

5. pneumonitis

• REGISTRATION STEP 1: Participants must not have active autoimmune disease requiring therapy within the past 6 months

• REGISTRATION STEP 1: Participants must not have an active infection requiring therapy

• REGISTRATION STEP 1: Participants must be ≥ 18 years old

• REGISTRATION STEP 1: Participants must not be pregnant or nursing because atezolizumab has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on protocol treatment and for five months after last dose of atezolizumab. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• REGISTRATION STEP 1: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Registration Step 1

• REGISTRATION STEP 1: Patient must be tested for hepatitis B within 28 days prior to Registration Step 1. Patient must not have active (chronic or acute) hepatitis B virus (HBV) infection. Patients may have past or resolved HBV infection. Active HBV is defined as having a positive hepatitis B surface antigen (HBsAg) test. Past or resolved HBV is defined as having a negative HBsAG test and a positive total hepatitis B core antibody (HBcAb) test

• REGISTRATION STEP 1: Patients must not have active hepatitis C virus (HCV) infection. Active HCV is defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test. Patient must have an HCV antibody test within 28 days prior to Registration Step 1. If the HCV antibody test is positive, the patient must also have an HCV quantitative RNA test within 28 days prior to Registration Step 1

• REGISTRATION STEP 1: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. Participants with localized prostate cancer who are being followed by an active surveillance program are also eligible

• REGISTRATION STEP 1: Participants must be offered optional participation in banking of specimens for future research

• REGISTRATION STEP 1: Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• REGISTRATION STEP 1: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• REGISTRATION STEP 2: Participants must be registered to Step 2 within 42 days after completion of radiation treatment. Participants must have received at least 44 Gy of radiation treatment

• REGISTRATION STEP 2: Participants must have no evidence of progression per RECIST 1.1 on CT scan of the chest, abdomen, and pelvis performed between 2 and 5 weeks after completion of radiation therapy

• REGISTRATION STEP 2: Any toxicities from radiation therapy must have resolved to < grade 2

• REGISTRATION STEP 2: ANC >= 1.5 x 10^3/uL (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: Platelet count >= 100 x 10^3/uL (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: Hemoglobin >= 9 grams/dL (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: AST and ALT =< 2.5 x IULN (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: Serum creatinine =< 1.5 x IULN OR measured or calculated creatinine clearance >= 40 mL/min (obtained within 28 days prior to Registration Step 2)

• REGISTRATION STEP 2: Participants must not have received steroids in doses of more than prednisone 10 mg daily or equivalent within 14 days prior to Registration Step 2

• REGISTRATION STEP 2: Participants must not have received a live vaccine within 28 days prior to Registration Step 2