pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer

NCT04090528 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 6 other identifiers: UW180372018-0938SMPH/MEDICINE/HEM-ONCA534260NCI-2019-07273Protocol Version 2/10/2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer. The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the percentage of patients experiencing objective anti-tumor effect as measured by PSA declines and/or objective radiographic responses. Participants must be 18 years of age or older and can expect to be on treatment for 2 years (32 cycles) and on study for up to 7 years (including 5 years of follow up via phone).

Conditions

Castration-resistant Prostate Cancer; Metastatic Cancer; Prostate Cancer

Keywords

immunotherapy; prostate cancer; vaccine; DNA vaccine; pTVG-HP; pTVG-AR; androgen receptor; prostatic acid phosphatase; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The expected 6-months PFS rate in Arm 1 (pTVG-HP DNA vaccine and Pembrolizumab) in this participant population is 20-30%. It is hypothesized that adding pTVG-AR DNA vaccine (Arm 2) will increase the 6-months PFS rate to at least 55%. The 6-month PFS rate will be calculated for each study arm along with the corresponding two-sided 95% confidence interval which will be constructed using the Wilson score method. Participants who withdraw from the study without a progression or death event before the 6-month assessment will be excluded from this analysis. The stratified (by randomization strata) Mantel-Haenszel test will be used to compare the 6-months PFS rates between study arms.

  6 months

Secondary Outcomes (7)

• Overall Objective Response Rate

  up to 2 years

• Prostate Specific Antigen (PSA) Response Rate

  Up to 2 years

• Median Radiographic Progression-Free Survival

  up to 2 years

• Median Duration of PSA and Objective Response

  up to 2 years

• Overall Survival (OS)

  up to 2 years

Study Arms (2)

Arm 1: One DNA vaccine

EXPERIMENTAL

100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles

Biological: pTVG-HP; Drug: Pembrolizumab

Arm 2: Two DNA vaccines

EXPERIMENTAL

100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4

Biological: pTVG-HP; Biological: pTVG-AR; Drug: Pembrolizumab

Interventions

pTVG-HP BIOLOGICAL

pTVG-HP is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP).

Arm 1: One DNA vaccine; Arm 2: Two DNA vaccines

pTVG-AR BIOLOGICAL

pTVG-AR is a plasmid DNA

Arm 2: Two DNA vaccines

Pembrolizumab DRUG

Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.

Also known as: Keytruda

Arm 1: One DNA vaccine; Arm 2: Two DNA vaccines

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All participants must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus GnRH analogue or antagonist treatment); subjects receiving Gonadotropin-releasing hormone (GnRH) analogue or antagonist must continue this treatment throughout the time on this study.
• Participants may or may not have been treated previously with a nonsteroidal antiandrogen. For participants previously treated with an antiandrogen, they must be off use of anti-androgen for at least 28 days before day 1 (for flutamide, apalutamide, enzalutamide, or other 2nd generation AR antagonists) or 6 weeks (for bicalutamide or nilutamide) prior to registration. Moreover, participants who demonstrate an anti-androgen withdrawal response, defined as a \> 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal.
• Participants must have a castrate serum level of testosterone (\< 50 ng/dL) within 6 weeks of day 1
• Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) bone scan criteria or RECIST 1.1 during or after completing last therapy:
• PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value \> 2.0 ng/mL.
• Measurable disease: \> 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions. The short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion
• Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan (or Sodium Fluoride (NaF) positron emission tomography-computed tomography (PET/CT)) consistent with metastatic disease compared to previous imaging during castration therapy. The increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI).
• Prior treatment with abiraterone or enzalutamide is permitted, but participants must have weaned to a daily corticosteroid dose equivalent of no more than 5 mg prednisone daily for at least 28 days prior to day 1.
• Life expectancy of at least 6 months
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Adequate hematologic, renal, liver, and coagulation function as evidenced by the following within 6 weeks of day 1:
• White Blood Cells (WBC) \>/= 2000 / mm3

You may not qualify if:

• Small cell or other variant (non-adenocarcinoma) prostate cancer histology, unless there is evidence that the tumor expresses PAP
• Participants may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than standard androgen deprivation therapy
• Concurrent bisphosphonate therapy is not excluded, however participants should not start bisphosphonate therapy while on this study; those participants already receiving bisphosphonate therapy should continue at the same dosing and schedule as prior to study entry
• Rapidly progressive symptomatic metastatic disease, as defined by the need for increased opioid analgesics within one month of registration for the treatment of pain attributed to a prostate cancer metastatic lesion; participants receiving opioids must receive approval from the PI for eligibility
• Treatment with any of the following medications within 28 days of day 1, or while on study, is prohibited:
• Systemic corticosteroids (at doses over the equivalent of 5 mg prednisone daily); inhaled, intranasal or topical corticosteroids are acceptable
• Prostate Cancer and spes (PC-SPES)
• Megestrol
• Ketoconazole
• α-reductase inhibitors - participants already taking 5-α-reductase inhibitors prior to 28 days prior to registration may stay on these agents throughout the course of therapy, but these should not be started while participants are on study
• Diethyl stilbesterol
• Abiraterone
• Enzalutamide
• Apalutamide
• Radium 223 (Xofigo®)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Merck Sharp & Dohme LLC: collaborator
• Madison Vaccines Incorporated: collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (2)

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Douglas G. McNeel, MD PhD
• Organization: University of Wisconsin - Madison

dm3@medicine.wisc.edu

(608) 263-4198

Study Officials

• Douglas McNeel, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomized, open-label, multi-institution phase II trial

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 16, 2019
• Study Start: October 21, 2019
• Primary Completion: November 24, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 5, 2025
• Results First Posted: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)