AGS-003 plus sunitinib shows promise in metastatic renal cell carcinoma

The addition of the novel agent AGS-003 to sunitinib induced memory T-cell responses that correlated significantly with improved OS in patients with metastatic renal cell carcinoma, according to phase 2 study results presented at the 28th annual Society for Immunotherapy of Cancer annual meeting.

The study evaluated AGS-003 (Argos Therapeutics) — an autologous dendritic cell immunotherapy containing co-electroporateddendritic cells with amplified autologous tumor RNA and synthetic CD40L RNA— in 14 patients with intermediate- and poor-risk metastatic renal cell carcinoma.

Patients received sunitinib (Sutent, Pfizer) in standard 6-week cycles. They also received AGS-003 every 3 weeks for five doses, followed by a dose every 12 weeks until progression.

Researchers used multi-color flow cytometry to measure patient immune responses after five doses of AGS-003. They then used an adaptation of the Binary Tree-Structured Vector Quantization algorithm to analyze correlations between immune responses and survival.

“This approach identified an AGS-003–induced central/memory cytotoxic T-cell (CTL) signature defined by the co-expression of CD28, CD27 and CCR7 receptors in the absence of CD45RA correlating with survival,” the researchers wrote. “Importantly, these CTL consist of proliferating CTL secreting multiple cytokines with lytic activity.”

Also, researchers identified a pre-treatment CTL signature and post-treatment CTL signature — both of which were lacking the CD28 receptor — that were inversely correlated with survival.

Median OS was 39.5 months. Three patients achieved partial response with prolonged booster phase dosing.

Four patients were still alive 4 years after registration. Two others with intermediate-risk disease continued treatment without disease progression 4 years after study registration.

“We believe that these additional findings from our phase 2 trial support the in vivo mechanism of action of AGS-003,” Charles Nicolette, chief scientific officer and vice president of research and development of Argos, said in a press release. “We also believe that this is the first demonstration in a clinical trial that the magnitude of an adaptive immune response following immunotherapy correlates with prolonged survival.”

Argos Therapeutics has initiated an open-label, randomized phase 3 trial to evaluate ARG-003 plus standard targeted therapy vs. standard therapy alone in 450 patients with newly-diagnosed metastatic renal cell carcinoma.

For more information:

DeBenedette M. Abstract #234. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 7-10, 2013; National Harbor, Md.

Disclosure: Researchers report employment with Argos Therapeutics Inc.