AGS-003 to Be Tested With Sunitinib as RCC Treatment

Edwin Posadas, MD

A trial (NCT01582672) that will pair a targeted treatment with a vaccine therapy for firstline treatment of renal cell carcinoma (RCC) is recruiting at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. The goal of the phase III trial is to help patients in this population gain long-term control of their disease, the institute said in a press release.

The experimental group in the international ADAPT trial will be taking the oral multi-kinase inhibitor sunitinib (Sutent), a standard treatment for the disease, along with investigational vaccine AGS- 003, an intradermally injected autologous dendritic cell immunotherapy. The control group will take sunitinib alone. The primary endpoint will be overall survival, while secondary endpoints will be progression-free survival, tumor response, and adverse events. The desired enrollment is 450 patients.

"This clinical trial asks one of the most important questions facing the field of kidney cancer at this time: Is there synergy between immunotherapy and targeted agents?" said Edwin Posadas, MD, co-investigator of the clinical trial, medical director of the Urologic Oncology Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, and associate professor in its Department of Medicine. "This study could be the first of many to truly redefine the approach investigators take to treat kidney cancer in the clinic."

The ADAPT trial was preceded by an open-label phase II study that examined AGS-003 plus sunitinib as a treatment for 21 patients with unfavorable-risk mRCC. The final median overall survival from the trial was 30.2 months, with approximately one-third of patients alive after nearly 4 years of follow-up.

In a secondary analysis of the study, the absolute number of a distinct AGS-003-specific cytotoxic T cell signature correlated with the improvement in survival. One patient who received long-term treatment with AGS-003 maintained multifunctional expression of the CD28 and CCR7 receptors with negative CD45RA expression for more than 3 years post-treatment. Survival for this patient exceeded the 30-month median in the trial.

The production of AGS-003 requires initial legwork, including upfront leukapheresis to collect dendritic cells. AGS-003 is then manufactured by transfecting the autologous dendritic cells with patient-specific RCC amplified RNA and synthetic, truncated human CD40 ligand RNA that has the potential to stimulate the immune system’s antineoplastic properties. After this process, the vaccine is reintroduced into the patient as an intradermal injection, eliciting a highly specific cytotoxic T-cell response through the initiation of a signaling cascade that causes the secretion of the cytokine IL-12.

Final data from the ADAPT clinical trial are expected in December 2015. If positive, the company is expected to submit a Biologic License Application to the FDA. In April 2012, the development of the agent received a Fast Track designation from the FDA.