The Lynx Group

Personalized Vaccine Promising When Added to Sunitinib in Patients with Metastatic Renal-Cell Carcinoma

March 2012, Vol 3, No 2

San Francisco, CA—A personalized form of immunotherapy added to sunitinib (Sutent) treatment prolonged survival to beyond 30 months in almost half of patients with newly diagnosed, unfavorable-risk metastatic renal-cell carcinoma (mRCC), according to the results of an open-label phase 2 study presented at the 2012 Genitourinary Cancer Symposium. Only approximately 1 in 10 patients with unfavorable-risk mRCC treated with sunitinib, the standard first-line treatment for clear-cell mRCC, survive past 30 months. This new therapy, AGS-003, uses the patients’ own dendritic cells, loads them with mRNA amplified from a specimen of their tumor, and then re-introduces the cells into the body to stimulate the proliferation of cytotoxic T-lymphocytes targeted to each patient’s tumor, explained Robert A. Figlin, MD, Samuel Oschin Comprehensive Cancer Institute, Cedars- Sinai Medical Center, Los Angeles, CA. The amount of AGS-003 produced generates up to 5 years of treatment for each patient. “AGS-003 combined with sunitinib is designed to overcome the inherent immune suppression in the tumor microenvironment and stimulate a durable clinical and immunologic response to the patient’s tumor,” said Dr Figlin.

To this end, AGS-003 with sunitinib was tested in 21 adults with newly diagnosed mRCC who received no previous systemic therapy. All patients had intermediate- or poor-risk disease according to various criteria. Patients received sunitinib (4 weeks on, 2 weeks off) combined with AGS-003 (5 doses, used 3 weeks apart, and then every 12 weeks) until disease progression. Among this group, 38% of patients demonstrated an objective (partial) response, and 73% of evaluable patients showed an immunologic response (ie, increases in the numbers of CD28-positive, CD45RA-negative T-cells). The estimated median overall survival (OS) was 29.3 months, and progression-free survival (PFS) was 11.2 months. By comparison, the PFS for sunitinib alone in similar patients is approximately 6 months, Dr Figlin noted.

“The addition of AGS-003 to sunitinib is associated with encouraging long-term OS beyond 30 months,” he said. Some 43% of the patients receiving the dual agents achieved an OS beyond 30 months. Recent data indicate that approximately 13% of patients with nonfavorable-risk mRCC treated with sunitinib survive beyond 30 months. To date, the 21 patients have received more than 150 doses of AGS- 003. The observed adverse events were consistent with the experience with single-agent sunitinib in this disease. The only adverse event attributable to AGS-003 was grade 1 injection-site reactions. No patients showed evidence of emergent autoimmune disease. These results support a planned international randomized phase 3 study that will compare AGS-003 plus standard therapy to standard therapy alone in 450 planned patients with newly diagnosed mRCC, Dr Figlin stated.

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