Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer

Summary

This study study aims to elucidate the immune responses to a shared antigen vaccine (PROSTVAC) and tumor specific antigens generated DNA vaccine in combination with checkpoint blockade using nivolumab (anti-PD-1), and ipilimumab (anti-CTLA-4). Additionally, the investigators will study the impact of the combination immunotherapy on peripheral T cell activation, as well as immune response in the tumor microenvironment. Finally, the investigators will evaluate the safety and tolerability to this novel personalized immunotherapy in combination with checkpoint blockade.

Conditions

• Metastatic Hormone-Sensitive Prostate Cancer

Interventions

BIOLOGICAL

PROSTVAC-V

-Replication-competent vaccinia virus which has been engineered to encode the sequences for a modified human prostate-specific antigen (PSA) and a triad of co-stimulatory molecules (TRICOM)

BIOLOGICAL

PROSTVAC-F

-Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.

DRUG

Nivolumab

-Nivolumab is a human monoclonal antibody (mAb)

DRUG

Ipilimumab

-Ipilimumab is a mAb blocking the inhibitory signal mediated by cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4), a protein receptor that downregulates the immune system.

BIOLOGICAL

Neoantigen DNA vaccine

Each DNA vaccination will be 1 mL vaccine administered intramuscularly. At each vaccination time point, patients will receive two injections at separate sites.

DEVICE

TriGrid Delivery System

-Electroporation device

PROCEDURE

Tumor biopsy

-Pre-treatment, post-treatment A (optional), and end of treatment

PROCEDURE

Peripheral blood

-At the time of pre-treatment biopsy, mid-treatment of chemo-ADT, at time of enrollment (prior to POSTVAC administration), mid-treatment A, mid-treatment B (multiple)

PROCEDURE

Fecal samples

-Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B

PROCEDURE

Leukapheresis

* Post-treatment A/pre-treatment B * Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1 * End of treatment

Sponsors & Collaborators

• Bristol-Myers Squibb

  collaborator INDUSTRY

• Prostate Cancer Foundation

  collaborator OTHER

• The Foundation for Barnes-Jewish Hospital

  collaborator OTHER

• Bavarian Nordic

  collaborator INDUSTRY

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Russell Pachynski, M.D. · Washington University School of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-09-14

Primary Completion

2022-04-01

Completion

2022-07-25

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations