SAN FRANCISCO—An immunotherapy (AGS-003) in combination with sunitinib may help prolong the lives of men with unfavorable risk, metastatic renal cell carcinoma (mRCC), according to new data from an open-label phase 2 study.

“We observed encouraging clinical and immunologic responses which correlated with prolonged survival,” said lead investigator Robert Figlin MD, Director of the Division of Hematology/Oncology at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles. “In this study, AGS-003 in combination with sunitinib was associated with a median overall survival longer than has been reported for sunitinib alone in unfavorable risk, metastatic RCC patients.”

He and his colleagues found that AGS-003 was well tolerated in combination with sunitinib.   Observed adverse events were consistent with expected sunitinib toxicities, with the notable exception being grade 1 injection site reactions in approximately 50% of study subjects. In addition, adverse reports and laboratory assessments for markers of autoimmune responses found no evidence of emergent autoimmune disease.

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The combination of AGS-003 plus sunitinib is designed to relieve immune suppression in the tumor itself and stimulate the patient’s immune response to the tumor. Each production of a patient’s fully personalized immunotherapy generates up to five years of treatment for each patient.

The study enrolled 21 patients (16 men) with newly diagnosed metastatic clear cell RCC. The median age was 56 years (range 22-68 years).  Following nephrectomy or metastasectomy to harvest tumor mRNA, autologous monocytes were collected by leukapheresis to produce RNA-loaded dendritic cells specific to each patient’s disease.  

Treatment consisted of six-week cycles of sunitinib, four weeks on and two weeks off, plus AGS-003. This fully personalized immunotherapy was administered as an intradermal injection every three weeks for five doses, and then every 12 weeks until progression in combination with sunitinib. To assess the induction of anti-tumor, CD28+ memory T cell responses, investigators evaluated immune responses at baseline and following five doses of AGS-003 using multiparametric flow cytometry.

Dr. Figlin, who presented the study findings at 2012 Genitourinary Cancers Symposium, said there were multiple partial responses observed with this combination regimen. Of 15 patients with serial immune assessments, 11 (73%) had increases in their CD28+ memory T cells. These immune responses correlated directly with prolonged survival. Overall, the median progression-free survival was 11.2 months, and the estimated Kaplan-Meier median overall survival was 29.3 months, based on follow-up through January 2012.

In addition, AGS-003 appeared to be well tolerated in combination with sunitinib, with no immunotherapy-related serious adverse events observed.

“Targeted therapy has been an important step but not a final step. A personalized vaccine offers the opportunity for hopefully long-term durable maintained remissions and even the possibility of a cure,” Dr. Figlin said.