Pembrolizumab and Radiation Therapy in Treating Patients With Intermediate or High-Grade Soft Tissue Sarcoma

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial
• Be ≥18 years of age on day of signing informed consent documents
• Have measurable disease based on RECIST 1.1
• Have newly diagnosed disease or localized recurrent or oligometastatic lesions that are candidates for radiation
• NOTE: Subjects may not have any prior systemic therapy or radiation for this sarcoma. They may have received systemic therapy and/or radiation for a different cancer
• NOTE: Oligometastatic disease will be defined as 3 or fewer detectable lesions with plans to radiate all detectable disease with conventionally fractionated radiation prior to resection
• Have an intermediate- or high-grade soft tissue sarcoma at the discretion of the reviewing Sarcoma pathologist
• The tumor must be at least 3 cm in maximum dimension for intermediate-grade tumors, or 1.5 cm in maximum dimension for high-grade tumors
• Have plans to undergo neo-adjuvant radiation and surgery with curative intent. A minimum of 45 Gy is necessary, planned to be administered over a minimum of 25 fractions
• Be willing to provide tissue from a newly obtained core incisional or excisional biopsy of a tumor lesion. Archival tissue from a recent clinical or research biopsy (within 90 days prior to Week 1 treatment) may be used in place of a fresh tissue biopsy
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale or > 70% on the Karnofsky scale. Evaluation of performance status is to be performed within 7 days prior to the date of enrollment
• Absolute neutrophil count (ANC) >= 1, 500/mcL (performed within 28 days of enrollment)
• Platelets >= 100, 000/mcL (performed within 28 days of enrollment)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 28 days of enrollment)
• Criteria must be met without erythropoeiten dependency and without packed red blood cell (pRBC) transfusion within last two weeks
• Serum creatinine = = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 28 days of enrollment)
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin = 1.5 ULN (performed within 28 days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = = 2.5 mg/dL (performed within 28 days of enrollment)
• International normalized ratio (INR) or prothrombin time (PT) = = grade 3) to pembrolizumab and/or any of its excipients
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
• Has current or a history of any distant metastatic disease (including brain)

*NOTE: An isolated or oligo-metastatic regional recurrence may be allowed if all other criteria are met, curative attempt is being pursued

• Has known history of (non-infectious) pneumonitis that required steroids, or has current evidence of pneumonitis
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with adherence to the requirements of the trial
• Is pregnant (positive urine pregnancy test within 72 hours prior to enrollment) or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA4 or anti-PD-L2 agent or w