Durvalumab and Grid Therapy for the Treatment of Non-small Cell Lung Cancer in Patients Who Progressed During or After Treatment With the PACIFIC Regimen

Inclusion Criteria:

Age >= 18 years
Primary non-small cell lung cancer treated previously on PACIFIC regimen (concurrent chemoradiation followed by durvalumab for stage III lung cancer)
Progression during durvalumab administration or within 6 months after completion of final durvalumab infusion
Body weight > 30 kg

Extracranial lesion >= 4 cm amenable to grid therapy

Patients with brain metastases are permitted to enroll
Patients with polymetastatic disease are permitted to enroll
Patients with local recurrence are permitted to enroll
Patients who do not have rapid polymetastatic progression (at the discretion of the enrolling physician)
Patients who have not had stereotactic body radiation therapy (SBRT) within 1 month of enrollment
Patients may receive conventional palliative radiation to other symptomatic metastatic disease
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Hemoglobin >= 9.0 g/dL (obtained =< 15 days prior to registration)
Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 15 days prior to registration)
Platelet count >= 100,000/mm^3 (obtained =< 15 days prior to registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN if total bilirubin is > 1.5 x ULN (obtained =< 15 days prior to registration)
Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 15 days prior to registration)
Creatinine OR glomerular filtration rate (GFR) =< 1.5 x ULN OR GFR > 60 mL/min for patients with creatinine > 1.5 x ULN (obtained =< 15 days prior to registration)
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
Persons able to become pregnant OR able to father a child must be willing to use an adequate method of contraception while on treatment and for 120 days after last treatment
Life expectancy >= 12 weeks
Provide written informed consent
Willingness to provide mandatory blood specimens for correlative research
Willing to return to Mayo Clinic for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:

Pregnant persons
Nursing persons
Persons of childbearing potential OR able to father a child who are unwilling to employ adequate contraception
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety of the prescribed regimens

Active autoimmune disease requiring systemic treatment, documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents

NOTE: Exceptions are allowed for:

Vitiligo
Resolved childhood asthma/atopy
Intermittent use of bronchodilators or inhaled steroids
Daily steroids at dose of =< 10mg of prednisone (or equivalent)
Local steroid injections
Stable hypothyroidism on replacement therapy
Stable diabetes mellitus on non-insulin therapy
Sjogren's syndrome

Uncontrolled intercurrent illness including, but not limited to:

Ongoing or active infection requiring systemic therapy
Interstitial lung disease
Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn's disease or others)
Known active hepatitis B (i.e., known positive hepatitis B virus [HBV] surface antigen [HBsAg] reactive)
Known active hepatitis C (i.e., positive for hepatitis C virus [HCV] ribonucleic acid [RNA] detected by polymerase chain reaction [PCR])
Known active tuberculosis (TB)
Symptomatic congestive heart failure
Unstable angina pectoris
Unstable cardiac arrhythmia or
Psychiatric illness/social situations that would limit compliance with study requirements (e.g., substance abuse)
History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Hypersensitivity to durvalumab or any of its excipients
Previous adverse event attributed to durvalumab or other PD-1 or PD-L1 directed therapy that led to drug discontinuation

History of grade >= 3 immune-related adverse event or any grade of immune-related neurologic or ocular adverse event while receiving immunotherapy

Note: Patients who had endocrine adverse events =< grade 2 are allowed to enroll if they are stable on appropriate replacement therapy and asymptomatic

Other active malignancy < 6 months prior to registration

EXCEPTIONS: Non-melanotic skin cancer, papillary thyroid cancer, prostate cancer, or carcinoma-in-situ of the cervix, or others curatively treated and now considered to be at less than 30% risk of relapse

Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product (IP)

Note: Local surgery of isolated lesions for palliative intent is acceptable
History of allogenic organ transplantation
History of active primary immunodeficiency
Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice)
Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Adjust wording as necessary and consider evaluating at screening for studies with known hepatotoxicity or other relevant requirements

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

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., computed tomography [CT] scan premedication)