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.
• Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
• Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
• 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 systematic palliative regimen for recurrent or metastatic disease
• Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
• Prior randomization or treatment in a previous MEDI4736 and/or tremelimumab clinical study regardless of treatment arm assignment or 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 MEDI4736
• 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 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 MEDI4736
• 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
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results