Phase 2 Trial of AGS-003 with Sunitinib for Advanced Renal Cell Carcinoma

Argos Therapeutics announced results from AGS-003-006, a Phase 2 study of AGS-003 in combination with sunitinib in patients with advanced renal cell carcinoma (RCC). The results showed a statistically significant correlation between anti-tumor memory T cell responses and overall survival. AGS-003 in combination with sunitinib overcame the immuno-suppressive environment of RCC and induced a tumor-specific multi-functional memory cytotoxic T lymphocyte (CTL) response.

AGS-003-006 was an open-label trial of AGS-003 in combination with sunitinib in patients with newly diagnosed, unfavorable-risk, metastatic clear cell RCC. Researchers sought to detect immune correlates by using multi-parametric flow cytometry to identify 16 unique RCC antigen reactive CTL subsets based on the expression of the surface markers CD28, CD45RA, CD27 and CCR7, present in blood draws collected prior to treatment with AGS-003 or sunitinib and after administration of five doses of AGS-003 in combination with sunitinib.  Each CTL subset was partitioned to an additional 64 functional subsets based on the expression of three cytokines (IFN-g, TNF-a, IL-2), lytic function (Granyme b, CD107 expression) and proliferation.

Correlates of CTL subsets with subjects' clinical lab characteristics were analyzed using an adaption of a binary tree-structured vector quantization (BTSVQ) approach used to cluster and visualize microarray data. The BTSVQ approach implemented a two-way unsupervised clustering that allowed each subject's clinical lab assessments, progression-free survival (PFS) and overall survival (OS) to be mapped back to immune responses to identify unique clustering patterns with clinical value. The data analysis identified one subset of CTL, with the CD8+CD28+CD45RA- memory CTL phenotype that trended with longer disease-free intervals and was a statistically significant correlate to overall survival.

AGS-003 is an immunotherapy that possesses tumor antigens, including the patient's unique mutated antigens, in order to produce a possible immune response, limit tumor escape, and induce immunologic memory relevant to each patient.

For more information, call (919) 287-6300 or visit www.argostherapeutics.com.