A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

This is a study to determine the clinical benefit (how well the drug works), safety, and tolerability of combining varlilumab and sunitinib. The study will enroll patients with metastatic clear cell renal cell carcinoma.

Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.

Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) some of which play a role in tumor growth and progression of cancer.

This study will evaluate the safety, tolerability and efficacy of the anti-CD27 antibody varlilumab in combination with sunitinib.

Eligible patients that enroll in the dose escalation portion of the study will be assigned to one of three dose levels of varlilumab in combination with 50 mg of sunitinib. The first phase of the study will test the safety profile of the combination and determine which dose of varlilumab will be studied in Phase ll\* of the overall study.

\*Note: This Study was terminated prior to initiation of Phase II.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.
2. Advanced metastatic disease
3. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
4. For Phase l, no more than 3 prior anticancer regimens (IL-2 or interferon do not count towards the total).
5. Measurable (target) disease.
6. Life expectancy ≥ 12 weeks.
7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment dose.
8. Must have available tumor tissue and consent to biopsy while on study.

Exclusion Criteria:

1. Prior therapy with an anti-CD27 antibody.
2. Previous treatment with sunitinib.
3. Use of any experimental immunotherapy.
4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
5. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
6. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
7. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
8. Active, untreated central nervous system metastases.
9. Active autoimmune disease or a documented history of autoimmune disease.
10. Active diverticulitis.
11. Significant cardiovascular disease including CHF or poorly controlled hypertension.
12. Impairment of gastrointestinal function or gastrointestinal disease that may alter the absorption of sunitinib.