**DTL is required for this study- Physicians must sign the toxicity grids

Current sites credentialed: SJMH (AA, Brighton, Canton, Chelsea), St. Mary's Livonia, Genesys

Eligibility Criteria:

Eligibility Criteria for Step 0 (Pre-Registration)

- Patient must be ≥18 years of age on day of consent.

- Patient must have an ECOG Performance Status of 0-2.

- Patient must have a diagnosis of pancreatic cancer and have successfully undergone a curative intent surgical resection and must have no evidence of recurrent disease as determined by the investigator.

NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors are excluded from enrolling.

- Patient must be planning to receive, be receiving or be within 8 weeks of having completed at least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy.Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 month course).

- Patient must have a known pathogenic or likely pathogenic germline or somatic mutation in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org.

Eligibility Criteria for Step 1 (Randomization)

- Patient must have met the eligibility criteria outlined in Section 3.1.

- Patient must have undergone at least 3 combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 months course).

- Central expert reviewer must have determined the patient eligible for randomization after review of local genetic testing reports.

- If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient has not previously undergone germline testing, the patient must agree to undergo germline testing.

- Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time of randomization as documented by baseline scans obtained ≤ 4 weeks prior to randomization.

- Patient must not have previously had evidence of progressive pancreatic cancer while receiving platinum-based therapy

- Patient must be ≥ 21 days (three weeks) from their last treatment (including chemotherapy or radiotherapy) but ≤ 56 days (eight weeks) from their last treatment. Patients who have received neoadjuvant and/or adjuvant radiotherapy are eligible.

- Patient must have recovered from any adverse events due to prior anti-cancer therapy (i.e., have no residual toxicities > Grade 1 with the exception of alopecia and/or neuropathy).

- Patient must not be receiving any other investigational agents at the time of randomization and while on protocol treatment.

- Patient must not have any history of allergic reactions attributed to compounds of similar chemical or biological composition to olaparib.

- Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.

- Patient must not have any uncontrolled gastrointestinal disorder that would, in the opinion of the investigator, interfere with the ingestion or absorption of olaparib.

- Patient must not be pregnant or breast-feeding due the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

-All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point,

2) has not undergone a hysterectomy or bilateral oophorectomy; or

3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

- Patients of childbearing potential and sexually active patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 1 month after the last dose of protocol treatment for female patients and for 3 months after the last dose of protocol treatment for male patients. Patients must also not donate sperm while on protocol treatment and for 3 months after the last dose of protocol treatment. Patients must also not breast-feed while on protocol treatment and for 3 months after the last dose of protocol treatment.

- Patient must have adequate organ and marrow function as defined below: (labs must be obtained ≤ 14 days prior to randomization):

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days

- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) except in patients with Gilbert’s syndrome. Patients with Gilbert’s syndrome may enroll if direct bilirubin ≤ 2.5 X ULN of the direct bilirubin

- Patient with Gilbert’s syndrome?

- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN

- Creatinine ≤ 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance > 50 mL/min/1.73 m2 .

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

- Patient must not have resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTc prolongation >500 ms, electrolyte disturbances, etc.) or have congenital long QT syndrome.

- Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir is prohibited. See Section 8.1.13 for more details.

- Patients who are being actively treated for an ongoing concurrent malignancy are ineligible, with the exception of those receiving adjuvant hormone therapies and those receiving topical therapies for skin cancers.

- Patient must not have, in the opinion of the investigator, any other concurrent medical condition that would prevent the patient from complying with the study procedures.

-Patient must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.

- Patient must have the ability to understand and the willingness to sign a written informed consent document, or have legally authorized representative provide authorization to participate.

- Patient must not have had major surgery within 2 weeks prior to randomization and patients must have recovered from any effects of any major surgery.

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: TH SJMH (Ann Arbor, Canton, Chelsea, Brighton), Livonia, Genesys, Hurley

Eligibility Criteria:

3.1.1 Patient must be ≥ 18 years of age.

3.1.2 Patient must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma that is MSIH/dMMR (microsatellite instability-high/mismatch repair deficient) as determined by one of three methods:

3.1.2.1 Deficient DNA Mismatch Repair Protein (MMR) Expression Status: MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR. dMMR may be determined either locally or by site-selected reference lab by CLIA-certified assay. NOTE: Loss of MLH1 and PMS2 commonly occur together.

3.1.2.2 Polymerase chain reaction (PCR) determined microsatellite instability.

3.1.2.3 MSI-H tumor status determined by next-generation sequencing.

3.1.3 Patient must have previously untreated localized gastric, or Siewert type II or III GEJ (gastroesophageal junction) adenocarcinoma. Tumors must be staged as T2 or greater primary lesion or be any T stage with the presence of positive locoregional lymph nodes- N+ (clinical nodes) without evidence of metastatic disease.

-Siewert Type II tumors: tumors located between 1 cm proximal and 2 cm distal to the GEJ. ?

-Siewert Type III tumors: tumors located between 2 and 5 cm distal to GEJ. 3.1.4 Patient must be amenable to surgical resection with therapeutic intent.

3.1.5 Patient must have an ECOG Performance Status 0-2.

3.1.6 Patient must demonstrate adequate organ and marrow function as defined below (these labs must be obtained ≤ 14 days prior to randomization): (Refer to most recent Protocol)

3.1.7 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

3.1.8 Patient must have no contraindications to receive one of the chemotherapy regimens: FLOT or mFOLFOX / CAPOX. 3.1.9 Patient must not have had prior potentially curative surgery for carcinoma of the stomach/GEJ.

3.1.10 Patient must not receive any other standard anti-cancer therapy or experimental agent concurrently with the study drugs.

3.1.11 Patient must have recovered from clinically significant adverse events of their most recent therapy/intervention prior to randomization.

3.1.12 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. 3.1.13 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

3.1.14 Patient must have chest/abdomen/pelvis CT completed within 4 weeks prior to randomization. 3.1.15 Patient may not have received prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA4 monoclonal antibody).

3.1.16 Patient must not have received any live vaccines within 30 days prior to randomization and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non\u0002live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist® are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events.

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST**

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Lehigh Valley Hospital 

Eligibility Criteria: 

3.1 Eligibility Criteria NOTE: Please see Section 4 for protocol-specific requirements for site registration.

3.1.1 Patient must be ≥ 18 years of age.

3.1.2 Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).

• Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes). NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.

• Patient may have calcified pulmonary nodules, and/or ≤ 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring ≤ 6 mm in maximal axial dimension.

• Patient’s primary tumor may be in place.

3.1.3 Patient must have received previous first-line chemotherapy that meets one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where  1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer. NOTE: First-line chemotherapy may have included any of the following regimens as listed in the NCCN Guidelines: FOLFOX (or equivalent), FOLFIRI (or equivalent), FOLFOXIRI, each with or without any of the following: bevacizumab, cetuximab, or panitumumab.

3.1.4 Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria 3.1.5 Patient must meet the following criteria for technical unresectability:

• A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments. NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease. NOTE: Patients who are deemed technically resectable but simultaneous biologically unresectable are not eligible.

**PLEASE SEE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST**

Pre-Registration (Step 0) eligibility:
-Pathologically proven diagnosis of squamous cell carcinoma (including variants) of the head/ neck; clinical stage T3-T4a, N0-2, M0 or T1, N1-2, M0
-Patient has undergone total resection of the primary tumor with curative intent
-Patient must have negative HPV status of the tumor as determined by p16 protein expression by IHC
-Patients with positive margins, nodal extracapsular extension, and/ or gross residual disease after surgery are not eligible
-Patient must not have had previous RT to the head and neck that would result in overlap of fields

Randomization (Step 1) eligibility:
-central determination of p53 mutation status must be resulted
-ECOG PS must be 0-1
-gross total resection of the primary tumor with curative intent was completed with 7 weeks prior

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED:
SJMH (Ann Arbor, Brighton, Canton, Chelsea), Sparrow, Saginaw, Livonia, LVHN, Holy Cross, St. John, Macomb, SJMO

Eligibility Criteria:

Eligibility for Step 1:

• Age = 18 years
• ECOG performance status of 0 or 1.
•  Patients must have oropharynx cancer that is p16-positive by immunohistochemistry with smoking status:

  =10 pack-years, stage T1-2N2-N3 or T3-4N0-3

  OR

  <10 pack-years, stage T4N0-N3 or T1-3N2-3. 

•  Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.  
•  Patients with a history of allergic reactions attributed to platinumbased chemotherapy agents are excluded.
•  Patients must not have had prior systemic therapy or radiation treatment for p16 positive OPSCC.
•  Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors.
•  Patients must not receive investigational agents within 4 weeks of enrollment or at any time while on study.
• Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded.

• Patients with uncontrolled inter-current illnesses which in the opinion of the investigator will interfere with the ability to undergo therapy including chemotherapy are excluded.

• Baseline organ and marrow parameters (must be obtained = 2 weeks prior to randomization).

• ANC = 1500/mm3 ANC

• Hgb = 8.0 g/dL Hgb

• Platelet count = 100,000/mm3

• Creatinine clearance of = 60 ml/min.

- Baseline liver function parameters (must be obtained = 2 weeks prior to randomization)

• Total bilirubin within 1.5 times the normal limits

• SGOT (AST) or SGPT (ALT) within 2.0 times the normal limits AND Alkaline Phosphatase within 1.5 times the normal limits

- Women must not be pregnant or breast-feeding

- Patients must have measurable disease as defined in Section 6.1.

- Patients must have tumor measurements with CT of neck and CT of chest (or CT of neck  and FDG PET/CT if standard of care) within 4 weeks prior to Step 1 randomization.

Eligibility Criteria for Step 2:

• Patients must have progression per RECIST criteria AND tissueproven progression on Arm B treatment within 12 months after completion of radiation therapy.
• ECOG performance status of 0 or 1.
•  Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.
• Patients must not have received non-protocol anti-cancer therapy after completion of radiation and chemotherapy.
• Baseline organ and marrow parameters (must be obtained = 2 weeks prior to registration).

-  ANC = 1500/mm3

-  Hgb = 8.0 g/dL

-  Platelet count = 100,000/mm3

-  Creatinine clearance of = 60 ml/min.

•  Baseline liver function parameters (must be obtained = 2 weeks prior to registration):

-  Total bilirubin within 1.5 times the normal limits

- SGOT (AST) or SGPT (ALT) within 2.0 times the normal limits AND Alkaline  Phosphatase within 1.5 times the normal limits

• Women must not be pregnant or breast-feeding
• Patients must have measurable disease as defined in Section 6.1.
• Patients must have tumor measurements with CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 2 registration.

Eligibility Criteria:

3.1.1 Patient must be ≥ 18 years of age.

3.1.2 Patient must have an ECOG Performance Status 0-2.

3.1.3 Patient must have differentiated thyroid cancer (DTC) with BRAF V600E mutation as determined by local testing, including the following subtypes (Note: results of a previous biopsy will be accepted): • Papillary thyroid carcinoma including histological variants of PTC such as follicular variant, tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin-like, trabecular, tumor with nodular fasciitis like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated.

• Follicular thyroid carcinoma including histological variants of FTC such as Hürthle cell, clear cell, insular, and poorly differentiated.

3.1.4 Patient must have been previously treated with or deemed ineligible for treatment with Iodine-131 for DTC, and must be receiving thyroxine suppression therapy

3.1.5 Patient must have had prior treatment with at least one of the following vascular endothelial growth factor receptors (VEGFR)-targeting tyrosine kinase inhibitor (TKI) agents for DTC: lenvatinib or sorafenib. NOTE: Up to two prior VEGFR-targeting TKI agents are allowed including, but not limited to lenvatinib and sorafenib.

3.1.6 Patient must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1·1 on chest CT (computed tomography) /abdominal/pelvis CT/MRI (magnetic resonance imaging) performed within 4 weeks prior to randomization.

3.1.7 Patient must have radiographic progression by RECIST 1.1 over any time interval on or after most recent prior systemic treatment.

3.1.8 Patient must not have any of the following cardiovascular and thromboembolic disorders or medical conditions:

• Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, or serious cardiac arrhythmias.

• Uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.

• Stroke, myocardial infarction, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months prior to randomization. Patients with more recent diagnosis of deep venous thrombosis are allowed if stable and treated with therapeutic anticoagulation for at least 6 weeks prior to randomization

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST **

**Credentialing must be completed prior to enrollment to main ALCHEMIST screening study (A151216)**

*DTL Required- Physicians must sign toxicity grid
CURRENT SITES CREDENTIALED:
Genesys, SJMH, Saginaw, Sparrow, St. Alphonsus, Lehigh, SJMO, St. Marys

-Patients must have undergone complete surgical resection of their stage IB (at least 4cm), II, or IIIA NSCLC and have had negative margins
-Patients must have no evidence of disease
-ECOG PS must be 0-1
-Patients must be registered to the ALCHEMIST-SCREEN (A151216)
-Non-squamous tumors must be EGFR and ALK wild-type
-Tumors must have PD-L1 status tested centrally
-Must not have prior treatment with an immune checkpoint inhibitor (anti-PD-L1, anti-CTLA4 monoclonal antibody)
-Patients must have adequately recovered from surgery and prior chemotherapy (grade 1 or less with exception of alopecia, ototoxicity and neuropathy)
-Patients must not require systemic corticosteroids equivalent to more than 10mg prednisone/d or other immunosuppressive meds

-Participants must have a pathologically-confirmed diagnosis of non-small cell lung cancer
-Participants must have advanced disease - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease.
-An EGFR exon 20 insertion mutation must be detected in the tumor tissue.
-Patients must have previously received at least one line of therapy for their advanced lung cancer. There are no restrictions on the maximum number of prior therapies allowed.
-Participants may not have received any prior treatment with therapies targeting PDL1, PD1 or CTLA4.
-ECOG performance status ?1
-Participants may not have clinically symptomatic brain metastases or leptomeningeal disease

-Patients must have histologically or cytologically confirmed stage IV non-squamous NSCLC (includes M1a, M1b, and M1c stage disease, AJCC 8th edition). Patients with T4NX disease (Stage IIIB) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation.

-Patients must have PD-L1 expression Tumor Proportion Score (TPS = 1% in tumor cells. The assay must have been performed by a CLIA (or equivalent) certified laboratory.

-Patients must have measurable or non-measureable disease as defined in Section 6.1.2. Presence of malignant pleural fluid alone is allowed as study eligibility.

-Patients must have an ECOG Performance Status of 0 to 1

-Patients must NOT have received the following:

---Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed since the prior therapy and registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed since completion.

---Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.

-Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.

-Patients with symptomatic brain metastases are excluded. Patients with treated or asymptomatic brain metastases are eligible if off steroids for at least 14 days prior to protocol treatment. Anticonvulsants are allowed.

-Patients with another active malignancy within the last 2 years are excluded. 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 five years are permitted.

-Patients must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.

-Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn’s disease, malabsorption,etc.)

-Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic

treatment.

-Patients must not have history of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, NYHA classification of 3, unstable angina or poorly controlled

arrhythmia, or myocardial infarction within 6 months prior to registration.

*Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED: SJMH, Livonia, Genesys, Sparrow, Saginaw, SJMO, Holy Cross

Eligibility Criteria:

Step 1 Eligibility Criteria – Concurrent Therapy

• Patient must be = 18 years old
• Patient must have one of the following: 
• Newly diagnosed stage IIIA/B/C NSCLC (per the AJCC 8th Edition) that is unresectable and is histologically and/or cytologically confirmed. 
• Nodal recurrence after surgery for early stage NSCLC. Please see Section 3.1.11 for associated requirements.
• Patient must have an ECOG Performance Status of 0 or 1.
• Body weight > 30 kg of patients.
• Patient should have a life expectancy greater than 12 weeks.
• Patient must have a baseline ECG obtained within 6 weeks of registration. 
• Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version v1.1, as defined in Section 6.1. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to registration.
• Absolute neutrophil count (ANC) = 1500 cells/uL
• White blood cells (WBC) counts = 2500/uL
• Platelet count = 100,000/uL
• Hemoglobin = 9.0 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.
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) = 3.0 x ULN.
• Patient must have acceptable organ and marrow function as defined below. These values must be obtained = 7 days prior to registration.
• Serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (see Appendix VI).
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5 x ULN.
• Patient must have pulmonary function tests (PFTs) with both FEV1 and DLCO = 40% of predicted, obtained within 5 months of registration.
• Patient should be expected to have Lung V20 of = 35%.
• Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
• No prior chemotherapy or radiation was ever administered for this lung cancer.
• Prior curative-intent surgery was at least 90 days prior to the nodal recurrence.
• No prior radiation was administered to the region of study cancer that would cause overlap of treatment fields.
• Patients who are Human Immunodeficiency Virus (HIV) positive may participate in the study IF they meet all of the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective.
• They must have a CD4 count of greater than 250 cells/mcL.
• They must not be receiving prophylactic therapy for an opportunistic infection.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients must not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration.
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until 90 days after the last dose of study treatment. All females of childbearing potential must have a negative blood test or urine study, with a minimum sensitivity 50 mlU/L or equivalent units of HCG, within 7 days prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must use accepted and highly effective method(s) of contraception during sexual intercourse for at least one week prior to the start of treatment, during protocol treatment, and continue for 90 days after the last dose of protocol treatment.
• Patient must not have any active, known or suspected autoimmune disease and neuromuscular paraneoplastic syndromes including, but not limited to myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, myositis, Guillain-Barré, systemic lupus erythematosus, and systemic sclerosis. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia), not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible.
• Patient must not have a history of 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 hepatitis C virus ribonucleic acid (HCV RNA).
• Patient must not have a known active tuberculosis infection.
• Patient must not have any severe infections within 4 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Patient must not have signs or symptoms of severe infection (sepsis) within 2 weeks prior registration.
• Patient must not have been treated with systemic immunostimulatory agents (including but not limited to interferon-a [IFN-a], interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to registration; or treated with an investigational agent within 4 weeks prior to registration (or within five half-lives of the investigational agent, whichever is longer).
• Unstable angina and/or congestive heart failure requiring hospitalization within 180 days prior to registration.
• Uncontrolled cardiac arrhythmia within 180 days prior to registration. weeks prior to registration (or within five half-lives of the investigational agent, whichever is longer).
• Patient must not have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Patient must not have been treated with systemic immunosuppressive medications (equivalent to > 10 mg prednisone per day) or other immunosuppressive medications within 7 days of registration. Inhaled or topical steroids and adrenal replacement steroid doses equivalent to > 10 mg prednisone per day are permitted in the absence of active autoimmune disease.
• Patient must not have had a prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Patient must not have a 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 within 4 weeks of registration.
• Patient must not have had any prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Patient with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. For example, patients must not have the following:
• Unstable angina and/or congestive heart failure requiring hospitalization within 180 days prior to registration.
• Uncontrolled cardiac arrhythmia within 180 days prior to registration.
• Patient must not have an uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Patient must not have received a live, attenuated vaccine within 4 weeks prior to registration.
• Patient must not have unintentional weight loss > 10% within 30 days prior to registration.
• Patient must not have had past radiation to the current intended treatment site.
• Patient must not donate blood while on study treatment.

Step 2 Eligibility Criteria – Consolidation

• Patients must not receive any non-protocol anti-cancer therapy after the end of chemo/radiation or during consolidation.
• Patients with any > Grade 2 non-hematologic or > Grade 3 hematologic toxicities must recover to grade 2 (or less) within 45 days after the end of concurrent chemo/radiation, with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with suspected cases of = Grade 2 pneumonitis (non-infectious) are not eligible for consolidative MEDI4736 (durvalumab) and will proceed onto follow-up instead.
• Patients must not have disease progression on the first post-treatment (for concurrent chemo/radiation) chest CT scan, which must be obtained within 14 days after the last dose of radiation therapy. If so, the patient is not eligible for consolidative MEDI4736 (durvalumab) and will proceed onto follow-up instead.