Prime-boost immunotherapeutic trial in men with biochemical recurrence after definitive local therapy for prostate cancer.
Authors: Stein Mark N. , Hawley Jessica E. , Pachynski Russell Kent , Zarrabi Kevin Kayvan , Dreicer Robert , Zibelman Matthew R. , Marshall Margaret A. , Jones Bethan , Wheeler Vicky , Sebastian Sarah , Bendall Jennifer , Anderson Katie , Shore Neal D. , Graff Julie N. 
Published: June 2023

TPS5119 Background: VTP-850 is a heterologous prime-boost immunotherapeutic consisting of 2 nonreplicating viral-vectored components: ChAdOx1-PCAQ, based on an adenoviral vector, and MVA-PCAQ, based on a modified vaccinia virus Ankara (MVA) vector. Both components encode the same 4 prostate cancer antigens: prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), six transmembrane epithelial antigen of prostate 1 (STEAP1), and 5T4, an oncofetal antigen. Preclinical studies in inbred, outbred, and HLA-A2 transgenic mice show that VTP-850 is highly immunogenic. Immune responses were measured in splenocytes using IFN-γ ELISpot assay, multiparameter flow cytometry, and targeted in vivo killing assays. The results indicate that VTP-850 can elicit T cell responses to each of the 4 encoded antigens, with the responses to PSA of greatest magnitude in all mouse strains studied. Intravenous administration of the boost resulted in a 6-fold increase in the magnitude of antigen-specific T cells induced and increased in vivo killing relative to the intramuscular boosting route1. Methods: This is a first-in-human multicenter Phase 1/2 trial to evaluate safety, PSA response rate and duration, and immunogenicity of VTP-850 in men with biochemical recurrence of prostate cancer after definitive local therapy. Phase 1 (15-18 participants) will follow a 3+3 design to determine the recommended phase 2 regimen; dose level of both ChAdOx1-PCAQ and MVA-PCAQ, and route of administration of MVA-PCAQ (IM or IV). Phase 2 will consist of 2 stages. In Stage 1, 19 additional participants will be enrolled at the chosen Phase 2 regimen. If 4 or more of the 25 participants (including the 6 Phase 1 participants who received the same regimen) have a PSA response (defined as ≥50% reduction in serum PSA compared to baseline at any time, measured twice consecutively, at least 2 weeks apart), Stage 2 will enroll 100 additional participants. Participants will be followed for 6 months or until start of new therapy (e.g. ADT) or until development of metastatic disease. Participants who have a PSA response during the 6 months follow up will be followed for up to an additional 18 months. Patients who have undergone primary therapy for prostate cancer and have biochemical recurrence are eligible. Patients must have nonmetastatic (M0) disease; serum PSA of > 0.3 ng/mL for participants with prior radical prostatectomy or serum PSA of 2 ng/mL above nadir for participants with prior external beam radiation or brachytherapy; PSA doubling time ≤12 months; and testosterone > 75 ng/dL. They cannot have received ADT within 6 months prior to Day 1 and cannot have received prior chemotherapy, immunotherapy or experimental agent for prostate cancer. The trial is open in the USA, with sites in Spain and Italy planned to open later in 2023. 1. Vardeu A et al 2022. Clinical trial information: NCT05617040 .