Dendreon, a biotechnology company, has reported positive data from its Protect or P-11 Phase III study suggesting that Provenge induces long-term memory immune responses that are durable and can be maintained following boosting. The results of the study also indicate that CD54 upregulation on antigen presenting cells, a measure of potency, is a correlate of immune activation.
P-11 is an ongoing Phase III clinical trial designed to evaluate the safety and biologic activity of Provenge in patients with non-metastatic androgen-dependent prostate cancer who have had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. Patients were randomized to Provenge or placebo following three months of hormone therapy. This study evaluated CD54 upregulation and peripheral immune responses in men enrolled in the trial.
Provenge or placebo was administered at weeks zero, two and four. A treatment booster infusion of Provenge or placebo was offered after confirmed PSA greater than or equal to 3ng/ml. Immune responses were measured pre-treatment, at weeks four and 13, and at four and 13 weeks following the booster infusion.
At the week zero dose of Provenge, the expression of CD54 on antigen presenting cells (APCs) was upregulated 5.8 fold. At the week two dose, it was 10.1 fold, significantly increased from week zero (p < 0.001). The increase in CD54 upregulation persisted at week four (10.7 fold) and at the time of the booster infusion (12 fold), the company said.
There was an increase in cellular immune response between pre-treatment and week four (p < 0.001), which persisted through 13 weeks after the booster infusion (p < 0.001). The Provenge booster infusions occurred from 0.2 to 5.5 years (median 1.1 years) after the week four dose.
David Urdal, chief scientific officer of Dendreon, said: We are encouraged to see that CD54 upregulation in APCs is maintained after boosting in men with androgen-dependent prostate cancer. We also are encouraged by these data which suggest that the immune response generated by Provenge is durable for a year or more after initial treatment and that it can be maintained following boosting.