Subjects will be randomized with equal probability to one of three arms, designated as P, V, and VG for statistical purposes. A general description of the intended i nterventions to be applied to the subjects randomized to these three arms is: Placebo PROSTVAC + Placebo Granulocyte Macrophage Colony- Stimulating Factor (GM -CSF) for Arm P, PROSTVAC + Placebo GM -CSF for Arm V, and PROSTVAC + GM -CSF for Arm VG. 2.1. Primary Objective T he primary efficacy objective is to ascertain whether there is evidence for either Arm V or Arm VG to have superior survival outcome relative to Arm P. 2.2. Secondary Objective T o ascertain whether a greater proportion of subject s randomized to Ar m VG or to Arm V remain event free at six months (or early termination) as compared to the subject s randomized to Arm P. 2.3. Exploratory Objectives T he Exploratory Objectives are: Bavarian Nordic, Inc. Statistical Analysis Plan Amendment 1 Protocol: BNIT -PRV -301 Date Issued: 29 June 2015 C onfidential 2 Revised: June 2015 •To evaluate whether HLA -A2 positive subject s have a larger survival effect size as compared to HLA-A2 negative subject s. •To model the radiological disease status over the first year of study participation. •To assess the role of post -treatment anti- cancer therapies as an alternative explanations for observed survival differences. •To compare the arms with respect to immune responses to immunizing antigen (PSA), as well as to non -vaccine containing prostate antigens, and tumor- associated antigens, and to assess whether immune responses are prognostic. •To compare the arms with respect to circulating tumor cell (CTC) levels. •To model the role of arm, potential baseline prognostic factors, including baseline subjectattributes and circulating tumor cells, immune responses, and the use of post-progression anti-cancer therapies as explanatory factors of survival. •To model the relationship between tumor regression and growth rates and duration of survival. 3.Investigational Plan 3.1. Overall Study Design and Plan BNI T-PRV-301 is a randomized, placebo-controlled, multi- center, Phase 3 efficacy trial of PROSTVAC in men with asymptomatic or min imally symptomatic, metastatic, castration - resistant prostate cancer. The study will consist of three periods: a Screening phase, followed by Treatment, and subsequently Long- term Follow -up (LTFU) phases. Fo llowing the completion of the Treatment phase (after the last dose of PROSTVAC -V/F +GM - CSF or placebo or early termination of treatment) of the trial, all subject s will automatically enter the LTFU phase with study visits occurring every six months. During L TFU subject s will receive standard -of-care treatment as determined by the Principal Investigator. The appropriate timing and the nature of any subsequent treatment will be at the discretion of the Principal Investigator. All treatments for mCRPC subsequent to the Treatment phase of the trial will be documented in the electronic case report form (eCRF) . This comprehensive data will be collected until study closure or death. A detailed schedule of assessments can be found in the protocol. 3.2.