Argos initiates Phase I/II trial with personalised immunotherapy drug

About 190,000 people worldwide are diagnosed with kidney cancer each year, including about 32,000 in the US. About half of US patients are eligible for surgical removal of the cancerous kidney, but if the tumour has already spread beyond the kidney, surgery is less effective. About 12,000 US patients die each year.

The drug candidate, AGS-003, is a second-generation dendritic cell-based therapy with immune response characteristics designed to stimulate the patient's immune system to target and destroy the patient's cancer cells.

Argos' approach taps into a powerful emerging trend that is sure to gain momentum in the near future. Personalised medicine's approach can directly examine and analyse the genetic basis of a disease and stratify the total population into different sub-sets each with common, but unique, disease characteristics.

Individuals diagnosed with familial breast, ovarian, colon cancer had been counselled in the past that they would receive standardised treatments and had limited options before their "condition" arrived.

Recent medical research indicates that medications, lifestyle changes and increased screening can mitigate some risk. An example is BRCA mutations where the carrier can have an increased lifetime risk of 85 per cent for developing breast cancer or up to 40 per cent increased risk of getting ovarian cancer.

Personalised medicine aims to identify these families at risk for cancer, heart disease, diabetes, etc.

Once identified by simple family history including a 3-generation pedigree or advanced genetic testing, the person can take preventative action.

This might include changes in diet, cessation of toxic habits, earlier screening, exercise, prophylactic medications or surgery.

To address the challenge of the unique genetic profile of each patient's cancer and the genetic mutations of that cancer, Argos loads the autologous dendritic cells with a patient's total tumour RNA.

Through this process, dendritic cells are enabled to recognise the complete antigenic repertoire of a particular patient's tumour, resulting in an immunotherapy personalised for a patient's specific disease.

"Metastatic renal cell carcinoma is a devastating disease with a poor prognosis for survival. There is still a dire unmet medical need for curative options that has unfortunately not been changed by recently approved therapies,"​ said Ted Logan, of Indiana University Cancer Center.

"Dendritic cell-based immunotherapy is a very promising approach; previous studies have demonstrated that using a patient's dendritic cells loaded with that individual's specific tumour RNA can lead to a primary immune response. I look forward to seeing whether the improved process used to manufacture AGS-003 will lead to an even stronger 'killer' T-cell response potent enough to target and destroy tumours."​

The AGS-003 Phase I/II trial will involve approximately 26 patients with newly diagnosed, metastatic renal cell carcinoma enrolled in the Phase I/II trial.

The primary objective of the trial is to measure T-cell responses to treatment with the AGS-003 immunotherapeutic.

The trial will also measure clinical antitumour activity, progression-free survival, and overall survival.

"The second clinical trial of AGS-003 in advanced renal cell carcinoma builds on the positive safety and activity results of our previous Phase I/II trial. In the current trial we are using an improved, second-generation AGS-003 to stimulate an enhanced immune response,"​ said Lothar Finke, chief medical officer and vice president of regulatory affairs for Argos.

"The successful demonstration of the safety and biologic activity of the product, in addition to showing the feasibility to produce and supply this individualised immunotherapy in a timely manner, will provide clinical proof of concept for our unique personalised approach to cancer immunotherapy."​