SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas

This is a multi-institutional phase II study of pembrolizumab in patients with advanced
sarcomas. This study will have two treatment groups, one group for patients with soft tissue
sarcoma and one group for patients with bone sarcoma.

Initial enrollment for this study included a total of 86 patients with soft tissue sarcoma
and bone sarcomas.

In the expansion portion, there will be an additional 30 patients with undifferentiated
pleomorphic sarcoma (UPS) and 30 patients with dedifferentiated or other high grade
liposarcoma (LPS) enrolled into the study.

Inclusion Criteria:

- Age ≥ 18 years (Age ≥ 12 years for patients with bone sarcomas).

- Histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic high
grade soft-tissue or bone sarcoma of one of the following subtypes: soft tissue
sarcomas (leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high
grade pleomorphic undifferentiated sarcoma/MFH and synovial sarcoma), and bone
sarcomas (Ewing sarcoma, osteosarcoma, and chondrosarcoma [de-differentiated or
mesenchymal]).

- ECOG Performance Status of 0 or 1.

- At least one site of measurable disease on CT/MRI scans as defined by RECIST 1.1.
Baseline imaging must be performed within 30 days of dosing.

- At least one site of accessible disease for pre- and post-treatment core biopsies for
at least 20 patients per arm on the expansion cohorts.

- Patients may have received 1-3 prior systemic therapies in the metastatic setting.

- Adequate organ function within 14 days of dosing

- Must be willing to provide and have available archival tissue for PD-L1 testing.

- Written, voluntary informed consent.

- Fertile men and women of childbearing potential must agree to use an effective method
of birth control from providing signed consent and for 120 days after last study drug
administration. Women of childbearing potential include pre-menopausal women and women
within the first 2 years of the onset of menopause. Women of childbearing potential
must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study.

- Effective methods of birth control include: surgically sterile, barrier device
(condom, diaphragm), contraceptive coil, intrauterine device (IUD), and abstinence.

- Life expectancy of >12 weeks.

- Patients with central nervous system disease are eligible for enrollment if they have
received prior radiotherapy or surgery to sites of CNS metastatic disease and are
without evidence of clinical progression for at least 4 weeks prior to screening, have
no evidence of new or enlarging brain metastases, and are off steroids for at least 7
days before first dose of pembrolizumab.

Exclusion Criteria:

- Prior systemic therapy targeting PD-1: PD-L1 axis.

- Patients who are curable by conventional multidisciplinary management.

- Patients with severe and/or uncontrolled concurrent medical disease that in the
opinion of the investigator could cause unacceptable safety risks or compromise
compliance with the protocol.

- Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
radiation for palliation < 2 weeks prior to screening or who have not recovered
adequately from side effects of such therapy.

- Patients who have active infections requiring therapy.

- Patients that are known to be positive for Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies), active Hepatitis B (HBsAg reactive), or Hepatitis C (HCV RNA
[qualitative] is detected); patients with negative Hepatitis C antibody testing may
not need RNA testing.

- Patients that have a known psychiatric or substance abuse disorder that would
interfere with cooperation with the requirements of the trial.

- Patients who received systemic anti-cancer treatment prior to the first dose of study
drug within the following time frames:

- Patients with active autoimmune disease or a documented history of autoimmune disease
or syndrome that requires systemic steroids or immunosuppressive agents. Patients with
vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients
that require inhaled steroids or local steroid injections would not be excluded from
the study. Patients with hypothyroidism not from autoimmune disease that is stable on
hormone replacement will not be excluded from the study.

- Women who are pregnant or nursing/breastfeeding.

- Known hypersensitivity to pembrolizumab or another mAb.

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

- Patients with untreated central nervous system disease. Patients with controlled
treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable
for 4 weeks are eligible.

- Inability to comply with protocol required procedures.

- Patients with medical conditions that require chronic systemic corticosteroid therapy
or require any other form of immunosuppressive medication. However, patients using
physiologic replacement doses of hydrocortisone, or its equivalent, will be considered
eligible for this study: up to 20 mg hydrocortisone (or 5 mg of prednisone) in the
morning and 10 mg hydrocortisone (or 2.5 mg prednisone) in the evening.

- Patients with the risk factors for bowel obstruction or bowel perforation (examples
include but not limited to a history of acute diverticulitis, intra-abdominal abscess,
abdominal carcinomatosis).

- Patients who have received a live vaccine within 30 days prior to the first dose of
trial treatment.