Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)
Condition: High Tumor Mutation Burden; High TMB (Tumor Mutation Burden); MSS (Microsatellite Stable)
MeSH terms: Neoplasms
Intervention: MK-3475
Intervention description: MK-3475 (pembrolizumab) 200 mg flat dose every 21 days
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Mutation load; Tumor mutation load; Mutation burden; Tumor mutation burden (TMB); Hypermutation; MSI Negative with Mutator Phenotype (High Tumor Mutation Burden); TMB (Tumor Mutation Burden)

Summary:

      This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor
      activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a
      mutator phenotype.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with microsatellite stable tumor and a tumor mutation burden (TMB) level
             measured at > 20 mutations per megabase pairs (MB)

          -  Have measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

          -  Adequate organ function as defined by study-specified laboratory tests

          -  Must use acceptable form of birth control through the study and for 28 days after
             final dose of study drug

          -  Signed informed consent form

          -  Willing and able to comply with study procedures

          -  Agree to have a biopsy of their cancer

          -  Patients with colon cancer must have received at least two prior cancer therapy
             regimens.

          -  Patients with other cancer types must have received at least one prior cancer therapy

          -  Progressive disease

        Exclusion Criteria:

          -  Patients with uncontrolled intercurrent illness, including but not limited to ongoing
             or active infection, systematic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia or psychiatric condition that would limit compliance with study
             requirements.

          -  Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior
             to the first dose of study drug

          -  Patients who have had radiation within 2 weeks prior to the first dose of study drug

          -  Patients who have undergone major surgery within 4 weeks of dosing of investigational
             agent

          -  Patients who have received another investigational product or investigational device
             within 4 weeks prior to receiving study drug

          -  Patients who have received any of the following concomitant therapy: Interleukin-2
             (IL-2), interferon, or other non-study immunotherapy regimens, immunosuppressive
             agents, other investigational therapies or chronic use of systemic corticosteroids
             within one week prior to first dose of study drug

          -  Patients who have received a live vaccine within 4 weeks prior to or after any dose of
             MK-3475 (exception: inactivated flu vaccines)

          -  Patients who have received growth factors, including but not limited to
             granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony
             stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug
             administration

          -  Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death
             protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4
             antibodies

          -  Patients with history of any autoimmune disease:inflammatory bowel disease, (including
             ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive
             sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis,
             central nervous system (CNS) or motor neuropathy considered to be of autoimmune
             origin.

          -  Patients who have known history of infection with HIV, hepatitis B, or hepatitis C

          -  Patients with evidence of interstitial lung disease

          -  Systemically active steroid use

          -  Patients on home oxygen

          -  Patients with oxygen saturation of <92% on room air by pulse oximetry

          -  Pregnant or lactating

          -  Conditions, including alcohol or drug dependence, or intercurrent illness that would
             affect the patient's ability to comply with study visits and procedures

          -  Patient with known active central nervous system metastases and/or carcinomatous
             meningitis.

          -  Patients with primary brain tumors.

          -  Requires any other form of systemic or localized antineoplastic therapy while on study

          -  Has any tissue or organ allograft

          -  Patients with history of allogeneic hematopoeitic stem cell transplant