ZymoGenetics, Inc. (NASDAQZGEN) announced positive final results from a Phase 2 clinical trial in patients receiving 2nd or 3rd line therapy for advanced renal cell carcinoma with the combination of recombinant Interleukin 21 (IL21) and Nexavar® (sorafenib) tablets. The combination demonstrated considerable clinical benefit, with an overall response rate (as assessed by an independent review) of 21%, a disease control rate of 82%, and progressionfree survival (PFS) of 5.7 months in this heavily pretreated population. Results were presented at the American Society of Clinical Oncology meeting.

“These results add to the case for efficacy and safety of IL21 when used with Nexavar in patients previously treated for renal cell cancer and point to a meaningful benefit of IL21 when used in combination with a targeted therapy,” said John Thompson, M.D., University of Washington and Seattle Cancer Care Alliance. “The combination of IL21 with Nexavar could be a promising treatment for renal cell cancer, particularly for patients after failure of prior therapies.”

Thirtythree patients were enrolled in the openlabel, multicenter Phase 2 clinical trial conducted at 14 sites in the U.S. and Canada. Study endpoints were safety, tumor response evaluated by RECIST (Response Evaluation Criteria In Solid Tumors) criteria, and PFS. Tumor response was assessed both by the investigator and by independent radiologic review.

Patients with metastatic renal cell cancer received 2nd or 3rd line therapy consisting of IL21 (30 mcg/kg on days 15 and 1519 of each 7week treatment course) in combination with the approved dose of Nexavar (400 mg PO BID continuously). The majority of adverse events and lab abnormalities were grade 1 or 2. Grade ≥3 adverse events considered possibly related to study drug (IL21 or Nexavar) and occurring in ≥3 patients included hypophosphatemia (42%), handfoot syndrome (24%), rash (27%), thrombocytopenia (9%), and neutropenia (9%). Overall, the combination of IL21 and Nexavar was tolerable in an out patient setting, with some patients staying on treatment for up to a year.

The independent review of tumor response was completed for 33 patients and showed 7 confirmed partial response (21%), 1 unconfirmed partial response (3%), 19 stable disease (58%), and 4 progressive disease (12%) and 2 unevaluable patients, for an overall disease control rate of 82% . Median PFS was 5.7 months or 24.6 weeks. The final Phase 2 results in renal cell cancer indicated that IL21 combined with Nexavar was well tolerated and is associated with meaningful antitumor activity both in terms of tumor response and duration of disease control (i.e. PFS) in patients who have failed prior therapy for advanced renal cell cancer.

About Interleukin 21 (IL21)

Despite the positive impact of targeted therapies on treatment for renal cell cancer, the efficacy of these agents appears to decrease beyond the firstline setting. There is an unmet need for novel therapies after failure of the targeted agents. IL21, a cytokine that enhances CD8+ T cell and NK cell activity, has singleagent antitumor activity (J Clin Oncol 262034, 2008). ZymoGenetics has worldwide rights to IL21 and is developing rIL21 for the treatment of renal cell carcinoma and metastatic melanoma.

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