| Eligibility |
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 =< 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) >= 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 X ULN OR direct bilirubin =< ULN for subjects with total
bilirubin levels > 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 X
ULN (performed within 28 days of enrollment)
- Albumin >= 2.5 mg/dL (performed within 28 days of enrollment)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants (performed
within 28 days of enrollment)
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants (performed within 28 days of enrollment)
- Female subjects of childbearing potential should have a negative serum pregnancy
within 72 hours prior to receiving the first dose of study medication
- All individuals of child-bearing potential must be willing to use an adequate method
of contraception, from the first dose of the study medication through 120 days after
the last dose of study medication
Exclusion Criteria:
- Has had prior radiation to affected area
- Has one of the following sarcoma subtypes where neoadjuvant chemotherapy is
established as practice at our institution: extra-skeletal Ewing's sarcoma, embryonal
rhabdomyosarcoma, alveolar rhabdomyosarcoma
* NOTE: Pleomorphic rhabdomyosarcoma is allowed. Bone sarcomas including osteosarcoma,
Ewing's sarcoma and chondrosarcoma are not allowed. Extra-skeletal Osteosarcoma is
considered a soft tissue sarcoma and is allowed.
- Has a diagnosis of immunodeficiency or has an active autoimmune disease that has
required systemic treatment in the past 2 years except replacement therapy (e.g.,
thyroxine, insulin, or physiologic corticosteroid)
- Is receiving systemic steroid therapy or any other form of immunosuppressive therapy
within 7 days prior to the first dose of trial treatment
- Has a known history of active TB (Bacillus tuberculosis)
- Hypersensitivity (>= 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 with an agent directed to another stimulatory or co-inhibitory 1-cell
receptor (eg, CTLA-4, OX 40, CD137)
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B (e.g., hepatitis B surface antigen [HBsAg]
reactive) or Hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
[qualitative] is detected) infection
- Has received a live vaccine or live-attenuated vaccine within 30 days of planned start
of study therapy. Administration of killed vaccines is allowed. Note: Any licensed
coronavirus (COVID-19) vaccine (including for emergency use) is allowed in the study
as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines,
or inactivated vaccines. These vaccines will be treated just as any other concomitant
therapy. Investigational vaccines (i.e., those not licensed or approved for emergency
use) are not allowed.
- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
or other circumstance that might confound the results of the study, interfere with the
subject's participation for the full duration of the study, such that it is not in the
best interest of the subject to participate, in the opinion of the treating
investigator or has not adequately recovered from any major surgery or has ongoing
surgical complications
- Has had an allogenic tissue/solid organ transplant
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