A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048)
Condition: Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms; Recurrence
Intervention: Pembrolizumab; Cisplatin; Carboplatin; 5-FU; Cetuximab
Intervention description: Pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 24 months.; Cisplatin 100 mg/m^2 IV on Day 1 of each 3-week cycle (6 cycle maximum).; Carboplatin at a target AUC 5 IV on Day 1 of each 3-week cycle (6 cycle maximum).; 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum).; Cetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each subsequent week until disease progression or unacceptable toxicity
Intervention MeSH terms: Carboplatin; Pembrolizumab; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 882.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1),; Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2); chemotherapy, 5-fluorouracil, cisplatin, carboplatin

Summary:

      Participants with recurrent or metastatic (R/M) squamous cell cancer of the head and neck
      (HNSCC) will be randomly assigned to receive pembrolizumab monotherapy [pembro mono],
      pembrolizumab plus chemotherapy with a platinum-based drug (cisplatin or carboplatin) and
      5-Fluorouracil (5-FU) [pembro combo], or cetuximab plus a platinum-based drug (cisplatin or
      carboplatin) and 5-FU [control]. The overall primary study hypotheses are as follows in all
      participants and in participants with Programmed Cell Death Ligand 1 (PD-L1) positive
      expression defined by Combined Positive Score (CPS) ≥1 and CPS ≥20: 1) pembrolizumab
      monotherapy prolongs progression free survival (PFS) per Response Evaluation Criteria in
      Solid Tumors Version 1.1 (RECIST 1.1) assessed by Blinded Independent Central Review (BICR)
      and prolongs overall survival (OS) compared to standard treatment, and 2) pembrolizumab
      combination with chemotherapy prolongs PFS per RECIST 1.1 assessed by BICR and prolongs OS
      compared to standard treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically- or cytologically-confirmed recurrent or metastatic head and neck
             squamous cell carcinoma considered incurable by local therapies

          -  No prior systemic therapy administered in the recurrent or metastatic setting (with
             the exception of systemic therapy completed > 6 months prior if given as part of
             multimodal treatment for locally advanced disease)

          -  Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx.
             Participants may not have a primary tumor site of nasopharynx (any histology)

          -  Measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Adequate organ function

          -  Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine
             needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to
             start of study treatment) is preferred but an archival sample is acceptable.

          -  Have results from testing of human papillomavirus (HPV) status for oropharyngeal
             cancer

          -  Female participants of childbearing potential should have a negative pregnancy test
             and 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 180 days after
             the last dose of study medication

          -  Male participants must agree to use an adequate method of contraception starting with
             the first dose of study medication through 180 days after the last dose of study
             medication

        Exclusion Criteria:

          -  Disease suitable for local therapy administered with curative intent

          -  Has progressive disease (PD) within six (6) months of completion of curatively
             intended systemic treatment for locoregionally advanced HNSCC

          -  Radiation therapy (or other non-systemic therapy) within 2 weeks prior to
             randomization or not fully recovered from adverse events due to a previously
             administered treatment

          -  Currently participating and receiving study therapy, or 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 study medication

          -  Life expectancy of <3 months and/or has rapidly progressing 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 medication
             (physiologic doses of corticosteroids may be approved after consultation with the
             Sponsor)

          -  Diagnosed and/or treated additional malignancy within 5 years prior to randomization
             with the exception of curatively treated basal cell carcinoma of the skin, squamous
             cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast
             cancers

          -  Has had an allogeneic tissue/solid organ transplant

          -  Active central nervous system metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years;
             replacement therapy is not considered a form of systemic treatment

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis

          -  Active infection requiring systemic therapy

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 180 days
             after the last dose of study medication

          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously
             participated in Merck MK-3475 clinical trial

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Received a live vaccine within 30 days of planned start of study medication