Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012)
Condition: Cancer; Solid Tumor
MeSH terms: Neoplasms
Intervention: Pembrolizumab
Intervention description: IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 297.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PD-1; PD1; PD-L1; PDL1

Summary:

      This study is being done to investigate the safety, tolerability and anti-tumor activity of
      pembrolizumab (MK-3475) in participants with advanced triple negative breast cancer (TNBC)
      (Cohort A), advanced head and neck cancer (Cohorts B and B2), advanced urothelial cancer
      (Cohort C), or advanced gastric cancer (Cohort D). Additionally, for Cohort D, data is
      presented for Asian Pacific (AP) participants. Only participants with programmed cell
      death-ligand 1 (PD-L1) expressing tumors were enrolled in Cohorts A, B, C and D. Participants
      in Cohort B2 were enrolled irrespective of PD-L1 status.

      The primary study hypothesis is that pembrolizumab is safe and well-tolerated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically-confirmed diagnosis of tumor that is recurrent,
             metastatic, or persistent:

               -  For Cohort A - triple negative breast cancer (estrogen, progesterone, and human
                  epidermal growth factor receptor 2 [HER2] negative)

               -  For Cohort B - squamous cell carcinoma of the head and neck (including human
                  papilloma virus (HPV)-positive head and neck squamous cell cancer).

               -  For Cohort C - urothelial tract cancer of the renal pelvis, ureter, bladder, or
                  urethra (transitional cell or non-transitional cell histology)

               -  For Cohort D - adenocarcinoma of the stomach or gastroesophageal junction

               -  For Cohort B2 - squamous cell carcinoma of the head and neck (both HPV-positive
                  and -negative head and neck squamous cell cancer)

          -  Any number of prior treatment regimens

          -  Measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1

          -  Female participants of childbearing potential must be willing to use 2 methods of
             birth control or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of study treatment

          -  Male participants must agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study
             treatment

        Exclusion Criteria:

          -  Currently participating in/has participated in a study of an investigational agent or
             using an investigational device within 4 weeks of the first dose of study treatment

          -  Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days prior to the first dose of study treatment

          -  Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1 or not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks
             prior to study Day 1 or not recovered from adverse events due to a previously
             administered agent

          -  Known additional malignancy that is progressing or requires active treatment excepting
             basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ
             cervical cancer that has undergone potentially curative therapy

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or
             documented history of clinically severe autoimmune disease, or syndrome that requires
             systemic steroids or immunosuppressive agents

          -  Evidence of interstitial lung disease

          -  Active infection requiring systemic therapy

          -  Known psychiatric or substance abuse disorders

          -  Pregnant, 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

          -  Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2,
             anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
             antibody

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or Hepatitis C

          -  Received live vaccine within 30 days prior to start of study treatment

          -  Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
             child) who is Investigational site or Sponsor staff directly involved with this trial,
             unless prospective Independent Review Board (IRB) approval (by Chair or Designee) is
             given allowing exception to this criterion for a specific participant