Abstract 2692: An ongoing Phase II trial of an adenovirus/PSA vaccine for prostate cancer

Abstract

Introduction and Objectives: Our Phase I adenovirus/PSA vaccine trial has proved that this vaccine is safe. We are conducting a Phase II clinical trial with two separate protocols for patients with recurrent or hormone refractory prostate cancer assessing toxicity, immune responses, and changes in PSA levels. Methods: In Protocol #1 men with recurrent prostate cancer following definitive initial treatment for their disease were placed in one of two arms: Arm A; men receive the vaccine alone at days 0, 30, and 60; Arm B; men receive the vaccine 14 days after the initiation of androgen deprivation therapy (ADT). In Protocol #2 men with hormone refractory disease receive the vaccine alone using the same 3 injection schedule. Each injection consists of 108 pfu of the Ad/PSA vaccine suspended in a collagen matrix. All patients return at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Results: To date forty four patients have been enrolled and have been followed a median of 12 months. The patients have a median age of 71.3 years, and median enrollment PSA levels of 0.62 ng/ml in Protocol #1 and 5.45 ng/ml in Protocol #2. In our preliminary results at this early stage of the trial, 100% of the patients in Protocol #1 and 67% of the patients in Protocol #2 demonstrated anti-PSA T cell responses above preinjection levels. Sixty four percent of the patients demonstrated an increase in PSA doubling time (PSADT). Conclusions: In an attempt to follow up on the success of our Phase I clinical trial of the Ad/PSA vaccine we have initiated a Phase II trial to investigate the therapeutic efficacy of the vaccine in men with recurrent prostate cancer, either following definitive therapy prior to other treatments or hormone refractory. Early results from the first four four patients demonstrate the induction of anti-PSA T cells responses in a high percentage of the vaccinated patients and increase in PSADT in more than half of the patients. No serious vaccine-related toxicities have been identified in the patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2692. doi:1538-7445.AM2012-2692

Past, Current, and Future of Immunotherapies for Prostate Cancer

“…In response to vaccination, 34% of patients generated anti-PSA antibodies, 68% developed anti-PSA T cell responses, 48% had an increased PSA doubling time, and 55% survived longer than predicted (53). An ongoing Phase II clinical trial (NCT00583024) investigating adenovirus/PSA responses in men with hormone refractory prostate cancer showed anti-PSA T cell responses were present in 100% of patients with recurrent disease and 67% in patients with hormone refractory disease (54). A newly recruiting phase I clinical trial will examine how mCRPC patients will respond to adenoviral PSA (ETBX-071), MUC1 (ETBX-061), and ETBX-051 (brachyury) vaccines (NCT03481816).…”

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice

“…An early stage analysis of an ongoing Phase II study with Ad 5 -PSA vaccine, using 2 different protocols for patients with recurrent or hormone-refractory prostate cancer, showed the induction of anti-PSA T-cell responses in a high percentage of vaccinated patients. In addition, there was an increase in PSA doubling time in about 64% of the patients [26]. These studies provide supportive evidence for the potential use of a second generation Ad 5 -PSA+PSCA bivalent vaccine for prostate cancer in clinical testing.…”

Immune-Based Therapies for Metastatic Prostate Cancer: An Update

“…In Protocol 2, men with hormone refractory disease received Ad5-PSA alone using the same three injection schedules, however Ad5-PSA was suspended in the gelfoam matrix. All of the patients in protocol 1 and 67 % of the patients in protocol 2 induced significant anti-PSA T cell responses; 64 % of the patients showed an increase in PSA doubling time [65].…”

“…A phase I trial of Ad5-PSA with or without gelfoam matrix in patients with PC, was shown to be safe (the primary endpoint of the trial), and anti-PSA T cell responses were induced in the majority of patients, however an increase rate rise in PSA (PSA doubling time) was noted in 50 % of patients [64]. A Phase II clinical trial of two separate protocols for patients with recurrent or hormone refractory PC were assessed for toxicity, immune responses, and changes in PSA levels [65]. In Protocol 1, men with recurrent PC following definitive initial treatment for their disease, either received Ad5-PSA alone on days 0, 30, 60, or received Ad5-PSA 14 days after the initiation of androgen deprivation therapy, 3 times, 30 days apart.…”