Phase I dose escalation trial of MVA-BN-PRO in men with nonmetastatic castration-resistant prostate cancer.

Abstract

193 Background: MVA-BN-PRO is an investigational prostate cancer immunotherapy comprising of a highly attenuated non-replicating vaccinia virus engineered to encode prostate specific antigen (PSA) and prostate acid phosphatase (PAP) proteins. Preclinical studies in mouse tumor models demonstrated vaccine-mediated induction of anti-PSA and PAP specific immune responses and anti-tumor activity. Results of the open-label multi-center evaluation in subjects with non-metastatic castration resistant prostate cancer are presented. Methods: Eligible subjects had documented prostate cancer with a rising PSA while on androgen suppression therapy and were chemotherapy naïve. Three cohorts of subjects were immunized subcutaneously receiving either 1, 2 or 4 injections of study drug (1 injection = 1×108 tissue culture infectious dose, TCID50) at monthly intervals for three months (treatment). If the vaccinations were tolerated, re-treatment with an additional 3 monthly vaccinations was administered at the same dose. Responders, defined as subjects with stable or declining PSA at week 29 compared with baseline, were offered a 1-year extended treatment of up to 12 monthly vaccinations. Subjects were followed for one year after their last vaccination. The primary endpoint was safety. Immune responses (humoral and cellular) to MVA-BN-PRO including the transgenes PSA and PAP were assessed by the ELISA and ELISPOT assays, respectively. Exploratory analyses included anti-tumor activity as evaluated by serum PSA levels and progression by bone scan, per investigator determined, or death. Results: Twenty-four subjects were dosed. All subjects completed the initial 3 vaccinations (treatment) and 21 subjects received 6 vaccinations (re-treatment). Seven responders received additional vaccinations during the extended treatment. No dose-limiting toxicities were reported. There were no reported ≥ Grade 3 treatment-related adverse events (AE). The most common related AEs were Grade 1 or 2 general disorders and administration site reactions. Conclusions: MVA-BN-PRO was well tolerated. Results from immune analysis and clinical activity measured by PSA levels or radiological progression will be presented. Clinical trial information: NCT00629057.

State of the Art in Locally Advanced and Recurrent Non-metastatic Prostate Cancer

“…All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥8 ng/ml within general disorders and administration site reactions. 84 The IMAAGEN core study is a phase II, multicenter study evaluating the ability of abiraterone plus prednisone to decrease PSA levels in patients with NM-CRPC with rising PSA. They have enrolled 131 patients with PSA value ≥10 ng/ml or PSADT ≤10 months at screening and 122 are evaluable.…”