Efficacy and Safety Study of Pembrolizumab (MK-3475) in Participants With Advanced Recurrent Ovarian Cancer (MK-3475-100/KEYNOTE-100)
Condition: Ovarian Neoplasms
MeSH terms: Ovarian Neoplasms
Intervention: Pembrolizumab
Intervention description: Administered at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 376.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Summary:

      This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in
      female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines
      of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting
      front line therapy). Participants will be enrolled into two separate cohorts based on the
      number of prior lines of treatment received for ROC. There will be no hypothesis testing in
      this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologically confirmed epithelial ovarian cancer, fallopian tube cancer or
             primary peritoneal cancer

          -  Has received a front line platinum-based regimen (administered via either intravenous
             or intraperitoneal route) per local standard of care or treatment guideline following
             the primary or interval debulking surgery with documented disease recurrence (note:
             Maintenance treatment following the front line treatment is permitted and counted
             together as part of the front line treatment)

          -  Has fulfilled the following additional requirements regarding prior treatments for ROC
             depending on the cohort participant is to be enrolled. Each participant must have
             documented evidence of clinical response or disease stabilization to the last regimen
             received.

               -  Cohort A: Has received 0 to 2 additional prior lines for treating ROC (or 1-3
                  total prior lines counting the front line) and must have a platinum-free interval
                  (PFI) of ≥ 3 to 12 months if the last regimen received is a platinum-based, or a
                  treatment-free interval (TFI) of ≥ 3 to 12 months if the last regimen received is
                  a non-platinum-based

               -  Cohort B: Has received 3 to 5 additional prior lines for treating ROC (or 4-6
                  total prior lines counting the front line) and must have a PFI of ≥ 3 months if
                  the last regimen received is a platinum-based, or a TFI of ≥ 3 months if the last
                  regimen received is a non-platinum-based

          -  Has measurable disease at baseline based on Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1 as determined by the central imaging vendor

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Has a life expectancy of ≥16 weeks

          -  Has provided a tumor tissue sample either collected from prior cytoreductive surgery
             or fresh newly obtained tumor tissue at screening

          -  Has adequate organ function

          -  Female participants of childbearing potential must be willing to use an adequate
             method of contraception for the course of the study through 120 days after the last
             dose of study drug

        Exclusion Criteria:

          -  Is currently participating in or has participated in a clinical study and received an
             investigational agent or used an investigational device within 4 weeks prior to the
             first dose of study treatment

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic 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 planned first dose
             of the study

          -  Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small
             molecule therapy, or radiation therapy within 4 weeks prior to the planned first dose
             of the study

          -  Has not recovered from AEs to ≤ Grade 1 or prior treatment level due to a previously
             administered agent

          -  Has epithelial ovarian cancer (EOC) with mucinous histology subtype

          -  Has a known additional malignancy that progressed or required active treatment within
             the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin that has undergone potentially curative therapy or in situ
             cervical cancer.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Participants with previously treated brain metastases may participate
             provided they have stable brain metastases

          -  Has known history of, or any evidence of active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has symptoms of bowel obstruction in the past 3 months

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the study

          -  Is pregnant or breastfeeding, or expecting to conceive children within the projected
             duration of the study, starting with the screening visit through 120 days after the
             last dose of study drug

          -  Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1,
             anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor
             (e.g. cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], tumor necrosis factor
             receptors OX-40 or CD137) or has participated in prior pembrolizumab (MK-3475) studies

          -  Has a known history of Human Immunodeficiency Virus (HIV)

          -  Has known active Hepatitis B or Hepatitis C

          -  Has received a live vaccine within 30 days of the planned first dose of the study