A personalized immunotherapeutic AGS-003 to treat metastatic kidney cancer (renal cell carcinoma) by Argos Therapeutics has shown that the experimental drug could be more effective than interferon-alfa.
AGS-003 uses Argos Therapeutics’ Arcelis. technology, and is a personalized, RNA-loaded, dendritic cell-based immunotherapy that is perfectly matched to each patient´s unique tumor burden.
Arcelis is Argos´ proprietary technology for personalizing RNA-loaded dendritic cell immunotherapies for HIV, other infectious diseases, and cancer.
This platform is based on optimizing a patient´s own (autologous) dendritic cells to trigger a pathogen- or tumor-specific immune response.
To address the challenge of the unique genetic profile of each patient´s disease and the genetic mutations of that disease, Argos loads the autologous dendritic cells with a sample of messenger RNA (mRNA) isolated from their disease.
Through this process, dendritic cells can potentially prime immune responses to the entire antigenic repertoire, resulting in an immunotherapeutic that is customized to the patient´s specific disease.
Argos Therapeutics released data from a Phase 2 trial that evaluated the safety, clinical response and immune response of AGS-003 treatment in newly diagnosed patients with metastatic renal cell carcinoma (mRCC).
According to results from the study, AGS-003 induced a tumor-specific immune response, performed better than interferon-? on a measure of progression-free survival, and was well tolerated.
“These results serve as preliminary proof-of-concept for AGS-003, demonstrating that this immunotherapy is able to induce an immune response to the very patient-specific tumor antigens that are targeted,” stated Charles Nicolette, Ph.D., chief scientific officer and vice president of Research and Development of Argos Therapeutics.
This study not only demonstrates a favorable safety profile and early signs of efficacy, but the results also compare favorably to historical results with standard immunotherapy approaches in mRCC patients. These results provide a strong basis for the ongoing Phase 2 trial evaluating the therapy in combination with sunitinib, he added.
In the study, the majority of patients suffered impaired cellular immunity to RCC tumor antigens. However, following AGS-003 treatment, the majority of patients experienced detectible cellular immunity to these same antigens, demonstrating that AGS-003 induced a tumor-specific immune response.
Additionally, 50% of patients had restored T cell-mediated interleukin-2 and interferon-? responses, indicating general immune reconstitution.
The median length of progression-free survival (PFS), from time of registration, was 5.6 months, in contrast to the historical median PFS for interferon-? of 5.1 and 2.5 months for intermediate and poor-risk subjects, respectively.
Forty percent of subjects experienced a clinical benefit, defined as either a partial response or stable disease.
AGS-003 was well tolerated, with no drug-related serious adverse events or grade 3/4 adverse events observed.
This open-label Phase 2 trial enrolled 20 evaluable, newly diagnosed post-nephrectomy patients with clear cell metastatic renal cell carcinoma.
Patients received intradermal injections of AGS-003 in the following sequence.
Argos is an immunotherapy company developing new treatments for cancer, infectious and autoimmune diseases, and transplantation rejection.
The company has generated multiple platform technologies and a diverse pipeline of products based on its expertise in the biology of dendritic cells — the master switch that turns the immune system on or off.