ZymoGenetics' IL-21 Phase 2 clinical trial in metastatic melanoma meets primary endpoint

ZymoGenetics, Inc. (NASDAQ:ZGEN) today announced positive results from a Phase 2 clinical trial in metastatic melanoma with recombinant Interleukin 21 (IL-21) as a single agent. The trial met the primary endpoint of efficacy, as measured by objective response rate or lack of early disease progression. Overall response rate was 23.1%, in evaluable patients, and median progression-free survival was 4.3 months. The results were presented at the American Society of Clinical Oncology meeting.

“Metastatic melanoma is difficult to treat and has no effective standard of care. We look forward to extending these observations in a randomized Phase 2 study with the selected dose of 30 mcg/kg.”

"The progression-free survival and response rate with IL-21 in patients with advanced melanoma are promising and warrant further investigation," said Teresa Petrella, M.D., NCIC Clinical Trials Group and Odette Cancer Centre in Canada. "Metastatic melanoma is difficult to treat and has no effective standard of care. We look forward to extending these observations in a randomized Phase 2 study with the selected dose of 30 mcg/kg."

The open-label, multi-center Phase 2 study was conducted by the NCIC Clinical Trials Group in Canada with the last subject enrolled in August 2009. A total of 40 patients were enrolled and treated with IL-21 using 3 dosing regimens. The initial cohort received 50 mcg/kg/day by outpatient intravenous bolus injection daily for 5 days in weeks 1, 3 and 5 of an 8 week treatment cycle. Cohort 2 received 30 mcg/kg/day in the same schedule, and Cohort 3 received 50 mcg/kg/day daily for 5 days in weeks 1 and 3 of a 6 week treatment cycle. Of the 40 patients treated, 10 patients received 50 mcg/kg/day, and 30 patients received 30 mcg/kg/day. The most common adverse events were fatigue, rash, fever, myalgia, anorexia, chills and nausea.

Thirty-nine of the 40 patients were evaluable for response, and 9 of the 39 (23.1%) had a confirmed partial response as measured by RECIST (Response Evaluation Criteria In Solid Tumors). In addition, 16 of the 39 patients (41%) had stable disease, and 14 of 39 (36%) had progressive disease. Two patients had 100% shrinkage of tumor target lesions, and responses were seen in patients with visceral disease, including liver metastases. Of the 30 patients treated with 30 mcg/kg/day (the dose selected for further study), 29 were evaluable for response, and 6 (21%) had a partial response, and 11 (38%) had stable disease.

The NCIC Clinical Trials Group in Canada evaluated their historical Phase 2 melanoma trial results with patients matching the IL-21 clinical trial entry criteria; the progression-free survival in the historical group was 1.58 months. The most commonly used treatment for patients with melanoma, dacarbazine, has shown median progression-free survival of 1.5 months and an overall response rate of less than 15%.

Median overall survival has not been reached, and patient survival data continue to be collected. Survival follow-up ranges from 5 to 24 months. Nineteen patients continue to be followed for survival.