DNA Vaccines + Pembrolizumab for Metastatic Prostate Cancer

Recruiting at 1 trial location

Overseen By Cancer Connect

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 21

Duration: 2 years

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial requires that you continue your current androgen deprivation treatment if you are on it. If you are taking certain medications like antiandrogens, you must stop them for a specific period before starting the trial. Other medications like systemic corticosteroids, abiraterone, and enzalutamide must be stopped 28 days before the trial.

What data supports the effectiveness of the treatment DNA Vaccines + Pembrolizumab for Metastatic Prostate Cancer?

Research shows that combining a DNA vaccine with pembrolizumab can lead to a decrease in prostate-specific antigen (PSA) levels, which is a marker of prostate cancer activity. In one study, 62% of patients treated with both the vaccine and pembrolizumab at the same time experienced a reduction in PSA levels, indicating a potential benefit of this combination treatment. ^{1 2 3 4 5}

Is the combination of DNA vaccines and pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) has been studied for safety in various conditions, including prostate cancer, and is generally considered safe, though it can have side effects. DNA vaccines like pTVG-AR and pTVG-HP have also been evaluated for safety in prostate cancer patients, showing manageable safety profiles. However, as with any treatment, there may be risks, and it's important to discuss these with your healthcare provider. ^{1 2 4 6 7}

How is the treatment with DNA vaccines and pembrolizumab unique for metastatic prostate cancer?

This treatment combines DNA vaccines targeting specific prostate cancer proteins with pembrolizumab, an immune checkpoint inhibitor, to enhance the body's immune response against cancer. Unlike traditional treatments, this approach uses a novel combination of immunotherapy strategies to potentially improve outcomes in patients with advanced prostate cancer. ^{1 2 4 5 8}

Research Team

Douglas McNeel, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adults with castration-resistant, metastatic prostate cancer who have been treated with androgen deprivation. They must be willing to use contraception, have a life expectancy of at least 6 months, an ECOG status of 0-2, no HIV/HTLV-1/hepatitis infections, and adequate organ function. Some will need biopsies and PET/CT scans.

Inclusion Criteria

My prostate cancer diagnosis was confirmed through a tissue examination.

I am currently on standard hormone therapy for my condition.

Participants must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding

Exclusion Criteria

Any other medical intervention or condition, which, in the opinion of the PI or treating physician, could compromise participant safety or adherence with the study requirements (including biopsies), or confound results of the study, over the treatment period

I have had my spleen removed or have an immune system disorder.

I am currently on bisphosphonate therapy but won't start it during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one or two DNA vaccines with pembrolizumab over 32 cycles, each cycle lasting 21 days, for up to 2 years or until radiographic progression

2 years

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up via phone

5 years

Treatment Details

Interventions

• Pembrolizumab
• pTVG-AR
• pTVG-HP

Trial Overview The study tests if using two DNA vaccines (pTVG-AR and pTVG-HP) with pembrolizumab (PD-1 blockade) increases the anti-tumor effect in patients compared to one vaccine plus pembrolizumab. Treatment lasts up to 2 years with additional follow-up.

Participant Groups

Group I: Arm 2: Two DNA vaccines Experimental Treatment 3 Interventions

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

Group II: Arm 1: One DNA vaccine Experimental Treatment 2 Interventions

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

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Madison Vaccines Incorporated

Industry Sponsor

Trials

4

Recruited

230+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Madison Vaccines, Inc

Collaborator

Trials

3

Recruited

190+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The combination of the immune checkpoint inhibitor atezolizumab and the tumor vaccine sipuleucel-T was found to be safe and well tolerated in 37 subjects with metastatic castration-resistant prostate cancer, with no severe toxicities reported.

While the objective response rate was low at 4.3%, the treatment did show some immune response benefits, including increased T-cell receptor diversity and immune responses to specific antigens, suggesting potential for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T. Dorff, T., Hirasawa, Y., Acoba, J., et al.[2022]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Reimagining Vaccines for Prostate Cancer: Back to the Future. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Phase 2 trial of T-cell activation using MVI-816 and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC). [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Detection of Microsatellite Instability via Circulating Tumor DNA and Response to Immunotherapy in Metastatic Castration-Resistant Prostate Cancer: A Case Series. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP [MVI-816]) in Patients With Progressive, Nonmetastatic, Castration-Sensitive Prostate Cancer. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand-binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer. [2021]