Durvalumab Followed by Chemoradiation and Consolidation Durvalumab for Stage III Non-small Cell Lung Cancer

Inclusion Criteria:

* Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Age ≥ 18 years at the time of consent.
* ECOG Performance Status of 0 or 1.
* Histological or cytological confirmation of stage III non-small cell lung cancer per AJCC, 8th edition, eligible for curative-intent concurrent chemoradiation. NOTE: subjects are not candidates for surgical resection either due to medical inoperability or surgically unresectable disease.
* Measurable disease according to RECIST 1.1 criteria.
* Plan for treatment with concurrent chemoradiation with a dose of radiation ranging from 54-66 Gy:

  * Planned mean dose delivery to the lung \<20 Gy
  * V20 \<35%
* No prior therapy for stage III NSCLC.
* Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
* Females of childbearing potential must have a negative serum pregnancy test within 24 hours of C1D1. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
* Females of childbearing potential must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.
* Men who are sexually active with WOCBP must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.
* Life expectancy of at least 12 weeks per investigator discretion.
* As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

* Prior therapy for stage III NSCLC
* Mixed histology with small cell lung cancer will not be allowed.
* Sequential chemoradiation will not be permitted.
* Induction and consolidation chemotherapy (separate from concurrent chemoradiation) will not be allowed.
* Prior exposure to anti-PD-1 or anti-PD-L1 antibodies including durvalumab.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

  * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  * Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
  * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* History of pulmonary fibrosis, interstitial lung disease, or pneumonitis requiring steroids.
* Active or prior documented autoimmune disease within the last 2 years. Patients with vitiligo, stable hypothyroidism, Grave's disease, or psoriasis not requiring systemic treatment are not excluded.
* Body weight \< 30 kg
* Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, COPD, allergic rhinitis).
* Active infection requiring systemic therapy.
* Uncontrolled current illness that in the opinion of the investigator renders the investigational treatment plan unsafe.
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
* Active other malignancy; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer.
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Treatment with any investigational drug within 30 days prior to registration.
* History of organ transplantation (including allogeneic stem cell transplantation).
* Other medical or psychiatric conditions that in the opinion of the site investigator would preclude safe participation in this protocol.

Eligibility Criteria for Consolidation Durvalumab

* Patients must have recovered from toxicities associated with prior chemoradiation to CTCAE \< Grade 2.
* Patients must not have progressed following chemoradiation therapy, as measured on imaging per RECIST 1.1.
* Confirmation of ECOG Performance Status of 0 or 1.
* Any grade pneumonitis from prior chemoradiation will not be permitted.