DNA Vaccines + Pembrolizumab for Metastatic Prostate Cancer

Not currently recruiting at 2 trial locations

Overseen By Cancer Connect

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: Androgen deprivation

Must not be taking: Corticosteroids, Abiraterone, Enzalutamide, others

Disqualifiers: Autoimmune disease, Brain metastases, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to treat metastatic prostate cancer that resists regular hormone therapy. Researchers aim to determine if one or two DNA vaccines, combined with pembrolizumab (a drug that aids the immune system in attacking cancer cells), can more effectively combat the cancer. Participants will receive treatments over two years to assess whether the combination reduces cancer markers or shows improvement in scans. Men with prostate cancer that has spread and does not respond to standard hormone treatments may be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the pTVG-AR DNA vaccine, when combined with pembrolizumab, has been safe in earlier studies. Preclinical research found that the pTVG-AR vaccine, which targets a specific part of prostate cancer cells, was well-tolerated without major safety concerns.

For the pTVG-HP DNA vaccine combined with pembrolizumab, past trials revealed that some patients experienced immune-related side effects, common with treatments that enhance the immune system. In one study, about 47% of patients experienced these side effects, but they were usually manageable. Another study with long-term follow-up found no serious side effects linked to the pTVG-HP vaccine.

Pembrolizumab is an FDA-approved drug for many cancers, indicating a well-known safety record. It helps the immune system find and destroy cancer cells. Overall, while side effects can occur, the vaccines and pembrolizumab have generally been safe in earlier research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic prostate cancer because they combine Pembrolizumab, a powerful immune checkpoint inhibitor, with innovative DNA vaccines, pTVG-AR and pTVG-HP. Unlike traditional hormone therapies or chemotherapy, which directly target cancer cells, these treatments aim to boost the body's immune response against the cancer. This is achieved through DNA vaccines that specifically target proteins associated with prostate cancer cells. By encouraging the immune system to recognize and fight cancer cells more effectively, these treatments have the potential to improve outcomes for patients with advanced prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic prostate cancer?

This trial will compare two treatment approaches for metastatic prostate cancer. In one arm, participants will receive the DNA vaccine pTVG-HP combined with pembrolizumab. Studies have shown that this combination can significantly lower PSA levels and reduce tumor size in some patients. In the other arm, participants will receive both DNA vaccines, pTVG-AR and pTVG-HP, alongside pembrolizumab. Early research found that pTVG-AR boosts the immune system's ability to fight prostate cancer cells, and when combined with pembrolizumab, it can enhance the body's defense against cancer. These findings suggest that combining these DNA vaccines with pembrolizumab could effectively treat advanced prostate cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Douglas McNeel, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7541575/

Multicenter Phase 1 Trial of a DNA Vaccine Encoding ... Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02861573

NCT02861573 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10729272/

Phase 2 trial of a DNA vaccine (pTVG-HP) and nivolumab ... The current trial was conducted to evaluate vaccination with PD-1 blockade, using nivolumab, in patients with early, recurrent (M0) prostate cancer.

4. withpower.com withpower.com/trial/dna-vaccines-pembrolizumab-for-metastatic-prostate-cancer-193e5

DNA Vaccines + Pembrolizumab for Metastatic Prostate ... 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 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S266637912300366X

Prostate cancer immunotherapy: Improving clinical ... A study in metastatic castration-sensitive PCa patients receiving ADT showed that pTVG-AR imparted Th1-type antitumor immunity in 47% of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04090528

Study Details | NCT04090528 | pTVG-HP DNA Vaccine ... This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with PD-1 blockade using pembrolizumab followed by treatment with ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-20-0945/56600/p/Multicenter-Phase-I-Trial-of-a-DNA-Vaccine

Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen ... Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825000319

Key considerations for a prostate cancer mRNA vaccine pTVG-HP DNA Vaccine with or without pTVG-AR DNA Vaccine and Pembrolizumab in Patients with Castration-Resistant, Metastatic Prostate Cancer, PAP and AR, DNA ...