Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)
Condition: Head and Neck Neoplasms
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
Intervention: Pembrolizumab; Placebo; Cisplatin; Accelerated Fractionation (AFX) Radiotherapy; Standard Fractionation (SFX) Radiotherapy
Intervention description: Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Normal saline or dextrose solution administered as an IV infusion Q3W; 100 mg/m^2 administered as an IV infusion Q3W; 70 Gray (Gy) given in 35 fractions over 6 weeks; 70 Gy given in 35 fractions over 7 weeks
Intervention MeSH terms: Cisplatin; Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 804.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Squamous Cell Carcinoma; Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD1; PD-1; PDL1; PD-L1; PDL2

Summary:

      The purpose of this study is to determine the efficacy and safety of pembrolizumab given
      concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in
      participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The
      primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in
      combination with CRT with respect to event-free survival (EFS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal
             p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell
             carcinoma. Participants with oral cavity tumors need to have unresectable disease.
             Participants with multiple synchronous tumors are not eligible for the study.

          -  Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker
             analysis from a core or excisional biopsy. If an excisional or incisional biopsy has
             been performed, participants remain eligible for the study provided the residual
             disease meets the staging criteria required for the trial (e.g., excisional biopsy of
             a lymph node with residual T4 primary). Prior surgical debulking, including
             tonsillectomy, for the head and neck cancer under study is not allowed.

          -  Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed
             by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1

          -  Is eligible for definitive CRT and not considered for primary surgery based on
             investigator decision

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed
             within 10 days prior to receiving the first dose of study therapy

          -  Female participants of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study therapy

          -  Female and male participants of reproductive potential must agree to use adequate
             contraception throughout the study period and for up to 180 days after the last dose
             of study therapy

        Exclusion Criteria:

          -  Is currently participating or has participated in a study with an investigational
             agent or using an investigational device within 4 weeks of the first dose of study
             therapy

          -  Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1),
             anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an
             agent directed to another co-inhibitory T-cell receptor or has previously participated
             in clinical studies with pembrolizumab

          -  Has received a live vaccine within 30 days prior to the first dose of study therapy

          -  Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as
             nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer

          -  Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical
             surgery for head and neck cancer under study

          -  Has not recovered from major surgery prior to starting study therapy

          -  Has known active Hepatitis B or C

          -  Has known history of Human Immunodeficiency Virus (HIV)

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             therapy

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years. Replacement therapy is not considered a form of systemic treatment.

          -  Has history of a diagnosed and/or treated hematologic or primary solid tumor
             malignancy, unless in remission for at least 5 years prior to randomization

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has had previous allogeneic tissue/solid organ transplant

          -  Has active infection requiring systemic therapy

          -  Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or
             radiotherapy or their analogs

          -  Is pregnant or breast feeding or expecting to conceive or father children throughout
             the study period and for up to 180 days after the last dose of study therapy