Last updated on June 2019

Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer


Brief description of study

This randomized pilot trial studies vaccine therapy and pembrolizumab in treating patients with prostate cancer that does not respond to treatment with hormones (hormone-resistant) and has spread to other places in the body (metastatic). Vaccines made from deoxyribonucleic acid (DNA), such as pTVG-HP plasmid DNA vaccine, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may find tumor cells and help kill them. Giving pTVG-HP plasmid DNA vaccine and pembrolizumab may kill more tumor cells.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To evaluate the safety of pembrolizumab in combination with pTVG-HP (pTVG-HP plasmid DNA vaccine) in patients with castration-resistant, metastatic prostate cancer.

II. To determine the 6-month progression-free survival and median time to radiographic progression in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP.

III. To evaluate the anti-tumor response rates (objective response rate and prostate specific antigen [PSA] response rate, using Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP.

SECONDARY OBJECTIVES:

I. To determine whether either treatment sequence, or prostatic acid phosphatase (PAP)-specific immune response, is associated with prolonged (6-month) radiographic progression-free survival.

II. To evaluate effects of schedule (concurrent versus delayed administration of pembrolizumab) on the magnitude of PAP-specific T-cell responses, programmed death receptor-1 (PD-1) expression on circulating T cells, and ligands for PD-1 (PD-L1) expression on circulating epithelial cells (CEC) and on tumor biopsies.

III. To determine the median time to radiographic progression using a concurrent administration schedule

TERTIARY OBJECTIVES:

I. To evaluate effects of treatment on number of circulating tumor cells. II. To evaluate PAP-specific antibody responses following treatment with pembrolizumab and pTVG-HP DNA vaccine (pTVG-HP plasmid DNA vaccine).

III. To determine whether either treatment sequence elicits immunologic antigen spread to other prostate-associated antigens.

IV. To determine whether pre-existing or vaccine-induced PD-L1 expression on CEC or tumor biopsies is predictive of objective clinical response.

V. To determine whether treatment elicits expression of other regulatory molecules on tumor-specific T cells (e.g. hepatitis A virus cellular receptor 2 [TIM3], B and T lymphocyte associated [BTLA], and lymphocyte-activation gene 3 [LAG3]) or tumor cells (e.g. tumor necrosis factor receptor superfamily, member 14 [HVEM], phosphatidyl serine, ligands for programmed death receptor-2 [PD-2] [PD-L2]).

VI. To determine whether PD-1-regulated antigen-specific T cells identified by trans vivo delayed-type hypersensitivity (DTH) testing can identify patients who develop objective clinical responses with PD-1 blockade therapy in combination with pTVG-HP.

VII. To determine whether changes in lymph nodes and soft tissue tumor lesions are observed by fluorothymidine F-18 (FLT) positron emission tomography (PET)/computed tomography (CT) after treatment with vaccine with or without pembrolizumab.

VIII. To determine if PD-1 inhibitor therapy in combination with pTVG-HP will change number and activity (SUV) in osteoblastic metastases as measured by NaF PET/CT.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pTVG-HP plasmid DNA vaccine intradermally (ID) every other week on days 1, 15, 29, 43, 57, and 71 and pembrolizumab intravenously (IV) over 30 minutes every 3 weeks on days 1, 22, 43, and 64.

ARM II: Patients receive pTVG-HP plasmid DNA vaccine ID as in Arm I and pembrolizumab IV over 30 minutes every 3 weeks on days 85, 106, 127, and 148.

After completion of study treatment, patients are followed up 3, 6, 9, and 12 months and then annually for 2 years.

ARM III: Extended Treatment. Patients received pTVG-HP + Pembrolizumab Extended Treatment

ARM IV: Extended Treatment. Patients receive pTVG-HP every two weeks, and Pembrolizumab every 4 weeks

Clinical Study Identifier: NCT02499835

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