A phase Ib/II trial of perioperative intratumoral MVA-BN-brachyury (MVA) plus systemic PROSTVAC and atezolizumab (Atezo) for intermediate-risk and high-risk localized prostate cancer (AtezoVax).

TPS382 Background: Many patients with intermediate or high-risk localized prostate cancer relapse after prostatectomy, identifying an unmet need. Cancer vaccines increase the infiltrating lymphocyte concentration in localized and metastatic prostate cancer (PMID 25255802, 29858218). We hypothesize that treatment with a combination of two vaccines plus PD-L1 inhibition will be safe and significantly stimulate immune infiltration within the tumor microenvironment. MVA is a modified vaccinia virus that is replication-deficient, inducing the generation of tumor antigen-specific killer T-cells. PROSTVAC is a poxviral based cancer vaccine using a vaccinia virus prime and fowlpox based boost along with co-stimulatory molecules B7.1, leukocyte function-associated antigen-3, and intercellular adhesion molecule-1. Methods: This study is a single-arm,, phase I/II investigator initiated trial (NCT04020094). Primary objectives: 1) Safety, 2) Quantitative change in infiltrating CD8+ lymphocytes between the biopsy and prostatectomy as measured by immunofluorescence. Secondary endpoints: 1) 6- and 12-month undetectable PSA rate; 2) PSA-PFS compared to institutional historic control. Inclusion criteria: unfavorable intermediate to very high-risk prostate adenocarcinoma (per NCCN). Exclusion criteria: non-adenocarcinoma histology and metastatic disease (including regional nodal metastasis). A total of 22 patients will be enrolled starting with a 6 patient safety lead in. Prostate MRI will be obtained prior to treatment. Treatment schema: 2 neoadjuvant cycles (Atezo + MVA + PROSTVAC), followed by prostatectomy then 6 additional adjuvant cycles (Atezo + PROSTVAC). Neoadjuvant cycle 1: atezolizumab (1200mg IV Q3wks), PROSTVAC-V (Prime, 2x108 Inf.U subcutaneous), MVA (2 x 108 Inf.U/0.5 ml, intra-tumoral injection, volume determined by MRI). Neoadjuvant cycle 2: atezolizumab, PROSTVAC-F (Boost, 1x109 Inf.U, subcutaneous), MVA. Adjuvant: atezolizumab and PROSTVAC-F. Clinical trial information: NCT04020094.