Anti-OX40 Antibody (MEDI6469) in Patients With Metastatic Colorectal Cancer

There will be three distinct cohorts of patients which will vary the timing of the MEDI6469
dose, starting three weeks before surgery and decreasing the interval before surgery by one
week with each cohort, as long as no dose-limiting toxicity attributable to the anti-OX40 are
observed.

Immunohistochemistry will be used to measure the immune cells within primary and metastatic
tumors when resected tissue is available, and surgically ablated tumors, giving each specimen
an "immune score". The primary endpoint of the study will be the difference in immune scores
of patients treated with anti-OX40 compared to historical controls (immune scores of
untreated patients). Secondary endpoints will include both clinical (survival) and
immunological data (specific measurements of immune cell populations based on flow cytometry
and immunohistochemistry).

Inclusion Criteria:

- Patients who will undergo staged liver resections are included in this study. In these
cases, preoperative MEDI6469 will be given prior to the initial procedure.

- Patients with small <3 cm tumors located >2 cm away from central bile ducts will be
considered for either radiofrequency ablation or resection, the choice of which will
be determined at the time of surgery.

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

- Laboratory values during preoperative assessment within the protocol specified 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.

- No clinical or laboratory coagulopathy

- Anticipated lifespan greater than 12 weeks

Exclusion Criteria:

- Metastatic disease outside of the liver that is not considered surgically resectable
or curable.

- 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.

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

- Enrollment in a clinical trial in which a different investigational agent is
administered within 4 weeks prior to the first dose of MEDI6469.