Hypofractionated Radiation Therapy to Improve Immunotherapy Response in Non-Small Cell Lung Cancer

Preclinical data suggest that radiation therapy may be uniquely suited to combine with immune
checkpoint inhibitors, since radiation can disrupt a tumor's physical barriers to T-cell
infiltration and augment antigen presentation, thus serving as an "in situ personalized
vaccine" to activate the immune system and potentially enhance the systemic response.

The rationale for this study is to determine the safety and efficacy of combined immune
checkpoint inhibitors and radiation therapy in metastatic non-small cell lung cancer
patients.

Inclusion Criteria:

- Stage IV metastatic Non Small Cell Lung Cancer

- Measurable disease of at least 1.5 cm in greatest dimension at least 2 non-irradiated
sites (except for lymph nodes, in which the short-axis dimension must be at least
1.5cm). There must be at least 1 visceral organ metastasis outside of the brain.

- History of prior cytotoxic chemotherapy (with or without concomitant radiation
therapy) with subsequent distant (metastatic) disease relapse, or progression of
disease while on chemotherapy.

- Participant must be planned to receive (or actively receiving) standard of care
checkpoint inhibitor immune therapy. For those patients actively receiving checkpoint
inhibitor immune therapy the duration of immune therapy at the time of enrollment must
be 4 months or less.

- Life expectancy greater than 3 months

Exclusion Criteria:

- Active autoimmune disease, primary immunodeficiency syndrome, HIV/AIDS, or hepatitis B
or C

- Oral corticosteroid dependency

- Uncontrolled or untreated active brain metastases/CNS disease

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia