Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease

Patients who will receive anti-PD-1/PD-L1 immunotherapy with at least 1 site of measurable
metastatic disease which will not be irradiated will be candidates for the study. Patients
will be randomized (1:1) to CBI combined with SBRT or CBI alone. SBRT at 9.5Gy x3 fractions
will be delivered within 1-21 days of the start of first cycle of CBI. The first six patients
will be treated and observed for toxicity in the safety run-in phase for 30 days after
radiation before continuing with further accrual. Radiation dose reduction is allowed if
necessary to meet tissue constraints (6Gyx3 Minimum Dose). Response rates will be determined
from the non-irradiated lesion/lesions. Blood draws will be obtained to analyze anti-tumor
immune responses.

Inclusion Criteria:

- Patient has one lesion that is treatable with SBRT.

- Patient has at least 1 site of measurable disease by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 criteria on computed tomography (CT) or Magnetic resonance
imaging (MRI) which will not be irradiated.

- Histological confirmation of malignancy (primary or metastatic tumor).

- Patient may have any prior therapy allowed aside from having had prior radiotherapy to
the treatment site.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

- Patient's screening laboratory values must meet protocol limits.

- Patient must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Patient has had chemotherapy or radiotherapy within 4 weeks prior to entering the
study or those who have not recovered from adverse events due to agents administered
more than 4 weeks earlier.

- Patient receiving any investigational or experimental agents other than immunotherapy.

- Patient who has had any prior radiotherapy to the treatment site(s).

- Patient is a pregnant woman (pregnant women are excluded from this study because
radiation treatment has known potential for teratogenic or abortifacient effects).

- Patient refuses to sign informed consent.