Anti-OX40 Antibody in Head and Neck Cancer Patients

This phase Ib clinical trial uses MEDI6469 at various dose intervals prior to definitive
surgical resection of patients with stage III and IV Oral Head and Neck Squamous Cell
Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of
preoperative MEDI6469 administration. In addition, tumor tissue and peripheral blood will be
obtained for exploratory immunologic end points including measurements of tumor infiltrating
immune cell populations based on flow cytometry and immunohistochemistry as well as
circulating immunological parameters that may correlate with changes induced by MEDI6469
administration.

Inclusion Criteria:

- Patients with treatment naive, resectable, stage III or IV squamous cell carcinoma of
the oral cavity, oropharynx, hypopharynx or larynx who are candidates for definitive
surgical resection followed by standard risk adapted adjuvant therapy.

- Histologic or cytologic diagnosis of a primary OHNSCC with no radiological evidence of
metastatic disease is acceptable. Patients with bone or cartilage invasion and any T
or N stage are acceptable.

- Patients with oral cavity primaries will be managed using conventional transoral or
transcervical techniques; oropharynx or hypopharynx tumor will be managed with
transoral robotic surgery; and larynx tumors (T3/T4 with thyroid cartilage invasion)
will be managed by either total laryngectomy or larynx preservation surgery.

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

- Laboratory values (performed within 28 days prior to enrollment) within protocol
defined range

- Ability to give informed consent and comply with the protocol. Patients with a history
of psychiatric illness must be judged able to understand the investigational nature of
the study and the risks associated with the therapy.

- No active gastrointestinal bleeding.

- Anticipated lifespan greater than 12 weeks.

Exclusion Criteria:

- Locoregionally unresectable or Metastatic disease (stage IVB)

- Active infection.

- Active autoimmune disease including patients with Inflammatory Bowel Disease as
determined by an autoimmune questionnaire.

- Previous treatment with mouse monoclonal antibodies

- Need for chronic maintenance oral steroids > 5mg prednisone daily equivalent.

- Any medical or psychiatric condition that in the opinion of the investigator would
preclude compliance with study procedures.