Immunotherapy Combined With Radiotherapy for Metastatic Sarcoma

This is a pilot study determining the feasibility of combination treatments, pembrolizumab and stereotactic ablative radiotherapy (SBRT) in subjects with soft-tissue sarcoma. These are subjects who have metastatic disease initially, or recurrent or progressive disease that is not eligible for curative surgery.

Inclusion Criteria: * Patients must have histologically or cytologically confirmed soft-tissue sarcoma, or a soft-tissue sarcoma with tumor mutational burden ≥10 mut/Mb. * Patient must either have started a checkpoint inhibitor immunotherapy regimen within 60 days, or have a soft-tissue sarcoma histology amenable to pembrolizumab therapy (inclusive of undifferentiated pleomorphic sarcoma \[formerly known as malignant fibrous histiocytoma\], myxofibrosarcoma, dedifferentiated liposarcoma or undifferentiated sarcoma \[unclassified histology\]). * Patients with soft-tissue sarcoma must have advanced disease (stage IV) or previously treated disease that has become progressive, recurrent, or metastatic, and either previously received first-line systemic therapy or been deemed ineligible to receive first-line systemic therapy. Staging is by AJCC 8th Edition. * Must not have disease amenable to curative intent surgery. * Must have at least 2 measurable lesions per RECIST v1.1 assessed by CT scan. A measurable lesion is defined to mean at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. * Must have at least 1 site of non-central nervous system (CNS) disease amenable to treatment with radiation therapy. This lesion may have been previously treated with radiation if the cumulative spinal cord dose will remain below a Biologically Effective Dose (BED)α/β 2Gy of 112 Gy (single fraction equivalent 14 Gy) and the radiation will be delivered at least 180 days after completion of the prior radiation course to the same site. BED will be calculated using the linear-quadratic formula: d \* f \* (1 + \[d / (α/β)\]), where d is the dose per fraction, f is the total number of fractions, and α/β is the property of irradiated tissue measured in Gray. * Must be age ≥ 18 years. Because initial and subsequent therapies for pediatric sarcomas (\