Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in Combination w/ Tremelimumab Squamous Cell Carcinoma of the Head and Neck
Condition: Recurrent/Metastatic Squamous Cell Carcinoma of Head & Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: MEDI4736; Tremelimumab; MEDI4736 + Tremelimumab
Intervention description: MEDI4736 monotherapy; Tremelimumab monotherapy; MEDI4736 + Tremelimumab combination therapy
Intervention MeSH terms: Durvalumab; Tremelimumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 267.0
Sex: All
Minimum age: 18 Years
Maximum age: 96 Years
Healthy volunteers: No
Keywords: Head and neck cancer; SCCHN

Summary:

      The purpose of this study is to determine the efficacy and safety of investigational medical
      products (MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab
      combination therapy) in the treatment of patients with recurrent or metastatic carcinoma of
      the head and neck who have progressed during or after treatment with a platinum containing
      regimen for recurrent/metastatic disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years;

          -  Written informed consent obtained from the patient/legal representative;

          -  Histologically confirmed recurrent or metastatic SCCHN; tumor progression or
             recurrence during or after treatment with only 1 systemic palliative regimen for
             recurrent or metastatic disease that must have contained a platinum agent; Patients
             who have only received chemo-radiation with curative intent for treatment of their
             locally advanced disease or recurrent disease are not eligible. Patients who received
             concurrent chemo-radiation as part of treatment of their recurrent disease are also
             not eligible.

          -  Written consent to provide newly acquired tumor tissue (preferred) or archival tissue
             for the purpose of establishing PD-L1 status.

          -  Confirmed PD-L1-negative SCCHN by Ventana SP263;

          -  WHO/ECOG performance status of 0 or 1;

          -  At least 1 measurable lesion at baseline;

          -  No prior exposure to immune-mediated therapy;

          -  Adequate organ and marrow function; Evidence of post-menopausal status or negative
             urinary or serum pregnancy test.

        Exclusion Criteria:

          -  Histologically confirmed squamous cell carcinoma of any other primary anatomic
             location in the head and neck;

          -  Received more than 1 regimen for recurrent or metastatic disease

          -  Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy
             for cancer treatment;

          -  Receipt of any investigational anticancer therapy within 28 days or 5 half-lives;

          -  Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy,
             targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose
             of study treatment;

          -  Major surgical procedure within 28 days prior to the first dose of Investigational
             Product;

          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
             criterion;

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of their assigned Investigational Product;

          -  History of allogeneic organ transplantation;

          -  Active or prior documented autoimmune or inflammatory disorders;

          -  Uncontrolled intercurrent illness;

          -  another primary malignancy

          -  Patients with history of brain metastases, spinal cord compression, or a history of
             leptomeningeal carcinomatosis;

          -  History of active primary immunodeficiency;

          -  Known history of previous tuberculosis;

          -  Active infection including hepatitis B, hepatitis C or human immunodeficiency virus
             (HIV);

          -  Receipt of live, attenuated vaccine within 30 days prior to the first dose of
             Investigational Product;

          -  Pregnant or breast-feeding female patients;

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs) using Fridericia's Correction

          -  Known allergy or hypersensitivity to Investigational Product.

          -  Any condition that, in the opinion of the Investigator, would interfere with
             evaluation of the IP or interpretation of patient safety or study results