Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
Condition: Head and Neck Squamous Cell Cancer
MeSH terms: Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell
Intervention: Pembrolizumab; Methotrexate; Docetaxel; Cetuximab
Intervention description: 200 mg intravenous (IV) on Day 1 of each 3-week cycle.; 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; 75 mg/m^2 IV on Day 1 of each 3- week cycle; 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Intervention MeSH terms: Docetaxel; Pembrolizumab; Methotrexate; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 495.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Squamous cell carcinoma; Head and neck carcinoma; Programmed Cell Death-1 (PD1, PD-1),; Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)

Summary:

      This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment
      (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and
      neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either
      pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is
      that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologically- or cytologically-confirmed recurrent disease not amenable to
             curative treatment with local or systemic therapy, or metastatic (disseminated) head
             and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and
             larynx that is considered incurable by local therapies

          -  Failure of prior platinum therapy

          -  Radiographically-measurable disease based on RECIST 1.1

          -  Tumor tissue available for PD-L1 biomarker analysis

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Adequate organ function

          -  Female participants of childbearing potential must be willing to use 2 methods of
             birth control or abstain from heterosexual activity for the course of the study
             through 120 days after last dose of pembrolizumab or through 120-180 days after the
             last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of
             care

          -  Male participants must agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after last dose of pembrolizumab or
             through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab,
             acccording to local standard of care

        Exclusion Criteria

          -  Disease is suitable for local therapy administered with curative intent

          -  Currently participating in or has participated in a study of an investigational agent
             or using an investigational device within 4 weeks prior to randomization

          -  Previously treated with 3 or more systemic regimens given for recurrent and/or
             metastatic disease

          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days prior to the first dose of study therapy

          -  Not recovered from adverse events due to therapy more than 4 weeks earlier

          -  Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day
             1, or not recovered from adverse events due to agents administered more than 4 weeks
             earlier

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to study Day 1

          -  Diagnosed and/or treated additional malignancy within 5 years of randomization, with
             the exception of curatively-treated basal cell or squamous cell carcinoma of the skin,
             and/or curatively-resected in situ cervical and/or breast cancers

          -  Active autoimmune disease that has required systemic therapy in the past 2 years with
             modifying agents, corticosteroids, or immunosuppressive agents

          -  Active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active, non-infectious pneumonitis

          -  Active infection requiring systemic therapy

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial therapy according to local standard of care

          -  Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously
             participated in a Merck pembrolizumab (MK-3475) trial

          -  Human immunodeficiency virus (HIV)

          -  Hepatitis B or C

          -  Live vaccine within 30 days of planned start of study therapy