Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer

Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy,
MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression.
Tumor assessments will be performed on computed tomography scans or magnetic resonance
imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be
assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8
weeks thereafter until treatment discontinuation due to progression or toxicity. All patients
will be followed every 3 months for survival after progression is confirmed.

Inclusion Criteria:

1. Age ≥18 years at the time of screening

2. Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx,
hypopharynx, or larynx).

3. A fresh tumor biopsy for the purpose of screening or an available archival tumor
sample. Tumor lesions used for fresh biopsies should not be the same lesions used as
RECIST target lesions, unless there are no other lesions suitable for biopsy.

4. No prior systemic chemotherapy for recurrent or metastatic disease

5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1 at enrollment

6. No prior exposure to immune-mediated therapy,

Exclusion Criteria:

1. Histologically or cytologically confirmed head and neck cancer of any other primary
anatomic location in the head and neck not specified in the inclusion criteria
including patients with SCCHN of unknown primary or non-squamous histologies (eg,
nasopharynx or salivary gland)

2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in
the primary treatment setting

3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days
prior to first dose of study treatment

4. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis