SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas
Condition: Soft Tissue Sarcoma; Bone Sarcoma
MeSH terms: Sarcoma
Intervention: Pembrolizumab
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 144.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the efficacy of pembrolizumab in patients with
      advanced sarcomas.
    

Eligibility criteria:

        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.