Study of Recombinant Interleukin 21 in Combination With Sorafenib for Metastatic Renal Cell Carcinoma

A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety and Pharmacokinetics of Recombinant Interleukin 21 (rIL-21) Administered Concomitantly With Sorafenib (Nexavar) in Subjects With Metastatic Renal Cell Carcinoma

The purpose of the study is to evaluate whether recombinant IL-21 used in combination with sorafenib is safe for patients with metastatic renal cell carcinoma (RCC).

This is a Phase 1/2 open-label dose-escalation study of rIL-21 given in combination with sorafenib to patients with metastatic RCC. The Phase 1 part of this study will estimate the maximum tolerated dose of rIL-21 given for 1 treatment course (consisting of two 5-day cycles of rIL-21) in combination with a standard dose of sorafenib administered during a 6-week treatment course. Increasing doses of rIL-21 will be studied sequentially in different groups of patients. The Phase 2 part of the study will further evaluate the safety and preliminary antitumor activity of rIL-21 at the dose recommended from Phase 1 in combination with sorafenib. Patients will be evaluated for safety over the course of the study. Disease evaluation (tumor restaging) will be performed during the last week of each 6-week treatment course. Patients with stable disease or better at this evaluation may go on to receive additional treatment courses. Patients may be in the study for 2 to 7 months.

Inclusion Criteria:

• Diagnosis of RCC of predominantly clear cell histology
• Either no prior treatment or a maximum of 2 prior treatment regimens for metastatic RCC that included no more than 1 treatment regimen targeting the vascular endothelial growth factor (VEGF) pathway (Phase 1 only)
• At least 1 but no more than 2 prior systemic therapies for metastatic RCC that included no more than 1 therapy targeting the VEGF pathway (Phase 2 only)
• Disease measurable per the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase 2 only)

Exclusion Criteria:

• Presence of acute infection or other significant systemic illness
• Central nervous system involvement by malignancy
• History of other cancer within 5 years
• Previously received rIL-21 or sorafenib