Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors
Condition: Solid Tumor, Adult
MeSH terms: Neoplasms
Intervention: Pembrolizumab 200 mg Q3W
Intervention description: Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: solid tumor, Pembrolizumab,

Summary:

      Phase II trial in which patients with metastatic solid tumors experiencing progression after
      first line standard chemotherapy or for which there is no standard chemotherapy, and for
      which pembrolizumab does not have an FDA or compendia listing approved indication, will
      receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have measurable disease based on RECIST 1.1.

          -  Be willing to provide consent for retrieval of archival tumor material tissue from a
             previously obtained core or excisional biopsy of a tumor lesion.

          -  Have a tumor presentation at screening for which pembrolizumab does not have an FDA
             approved indication for commercial use.

          -  Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication.

        Expansion cohort - additional criteria

          1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed
             standard treatment or is recurrent, or for which standard chemotherapy is
             contraindicated or refused by patient.

          2. Sufficient tissue is available for correlative studies

          3. MSI studies have been performed, either by immunohistochemistry or next generation
             sequencing and results show that patient is MS low or stable.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy, or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Has a diagnosis of immunodeficiency or 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 additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has a known history of active Bacillus Tuberculosis

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable. This exception does not include carcinomatous meningitis which is
             excluded regardless of clinical stability.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs).

          -  Has immunohistochemically proven mismatch repair deficient cancer

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Evidence of interstitial lung disease.

          -  Has an active infection requiring systemic therapy.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant 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.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.