Vaccine +/− Nivolumab for Prostate Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Corticosteroids, Herbal supplements, others

Disqualifiers: Prior prostate treatment, Active cardiac disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine approach for treating prostate cancer, using a combination of a DNA vaccine and drugs that enhance the immune system's ability to fight cancer cells. Participants will receive various treatment combinations, including Nivolumab (an immunotherapy drug), to determine which most effectively boosts the body's defenses after hormone therapy. Men with newly diagnosed, high-risk prostate cancer who plan to undergo prostate removal surgery may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids, PC-SPES, and herbal supplements that affect testosterone, among others. However, if you are already taking 5-α-reductase inhibitors, you can continue them during the trial. There is no specific washout period mentioned for most medications, except systemic corticosteroids, which should not be taken within 3 months of registration.

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

Research shows that the treatments under study appear safe. Degarelix, a common treatment for prostate cancer, effectively manages testosterone levels and matches the safety of other standard treatments. It is usually well-tolerated with a low risk of serious heart problems.

When combined with the pTVG-AR vaccine, studies aim to boost the immune response against prostate cancer. This combination is still under safety evaluation, but each component has been tested individually and is generally well-tolerated.

Adding Nivolumab, a drug that enhances immune system function, has shown positive results in early trials with manageable side effects. Similarly, Cemiplimab, another immune-boosting drug, has been used safely in other cancer treatments.

The combination of Degarelix, pTVG-AR, Cemiplimab, and Fianlimab is newer, but each component has been manageable for patients. The current phase of the trials suggests these treatments are safe enough for testing in larger groups.

These findings are encouraging, but monitoring for potential side effects during the trial remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they explore novel combinations that could enhance the body's immune response against cancer cells. Unlike the standard hormone therapy, which usually focuses on reducing testosterone levels, these treatments combine Degarelix with various immunotherapies like pTVG-AR, Nivolumab, Cemiplimab, and Fianlimab. Each of these combinations potentially boosts the immune system's ability to target and destroy cancer cells more effectively. Notably, pTVG-AR is a DNA vaccine intended to stimulate an immune response specifically against prostate cancer antigens, while Nivolumab and Cemiplimab are checkpoint inhibitors that help unleash the immune system. This multi-pronged approach could offer a more powerful and targeted attack against prostate cancer than existing treatments.

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

Research has shown that combining Degarelix with the pTVG-AR vaccine, which participants in this trial may receive, can slow prostate cancer growth and extend patient survival. One study found that 83% of patients who received this combination were alive after three years, compared to 76% of those who only received standard hormone therapy. In this trial, some participants will also receive Nivolumab, a drug that helps the immune system fight cancer and might enhance these results. Similarly, other participants will receive Cemiplimab, another drug that boosts the immune system and has shown promise in helping patients achieve long-term remission in aggressive cancers. Fianlimab, which targets a different part of the immune system, could also improve outcomes by helping the body fight cancer cells more effectively. Overall, these treatments aim to enhance the body's natural ability to attack cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Christos Kyriakopoulos, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Men with newly diagnosed, high-risk prostate cancer who are scheduled for prostatectomy can join. They should have a Gleason score of 7 or higher and PSA > 20 ng/mL, be in good physical condition (ECOG 0-1), and have adequate organ function. Participants must consent to blood draws, use barrier contraception if sexually active, and not have HIV, HTLV-1, Hepatitis B/C or other cancers.

Inclusion Criteria

Willingness to use barrier contraceptive methods if sexually active

I have no history of specific infections.

My prostate cancer has been confirmed by a tissue examination.

Exclusion Criteria

Concurrent enrollment in other investigational treatment studies

I have not had major surgery in the last 4 weeks.

I am not on any other experimental drugs or cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive degarelix and pTVG-AR, with or without T-cell checkpoint blockade, prior to prostatectomy

8 weeks

Multiple visits for administration of degarelix, pTVG-AR, and checkpoint inhibitors

Prostatectomy

Participants undergo prostatectomy to assess pathological response

Up to 3 months

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival

Up to 15 months

What Are the Treatments Tested in This Trial?

Interventions

• Degarelix
• Nivolumab
• pTVG-AR

Trial Overview The trial is testing the effectiveness of a DNA vaccine targeting the Androgen Receptor (pTVG-AR) alone or combined with Nivolumab after initial hormone therapy in patients undergoing surgery for prostate cancer. The goal is to boost T-cells that fight cancer.

How Is the Trial Designed?

Group I: Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab Experimental Treatment 4 Interventions

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64 * Fianlimab 1600 mg IV administered at days 1, 22, 43 and 64

Group II: Arm 4: Degarelix and pTVG-AR and Cemiplimab Experimental Treatment 3 Interventions

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64

Group III: Arm 3: Degarelix and pTVG-AR and Nivolumab Experimental Treatment 4 Interventions

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Nivolumab 240 mg IV administered at days 29, 43, 57 and 71

Group IV: Arm 2: Degarelix and pTVG-AR Experimental Treatment 3 Interventions

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71

Group V: Arm 1: Degarelix Active Control 2 Interventions

\- Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57

Degarelix is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Firmagon for:

• Advanced hormone-dependent prostate cancer

Approved in United States as Firmagon for:

• Advanced prostate cancer

Approved in Canada as Firmagon for:

• Hormone-sensitive prostate cancer

Approved in Japan as Firmagon for:

• Prostate cancer

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Madison Vaccines Incorporated

Industry Sponsor

Trials

4

Recruited

230+

Madison Vaccines, Inc

Collaborator

Trials

3

Recruited

190+

Published Research Related to This Trial

Vaccine therapy for prostate cancer, particularly using autologous dendritic cells, has shown promising results, significantly prolonging overall survival in patients with advanced hormone-refractory prostate cancer compared to placebo.

Most vaccine approaches have mild side effects and are being further explored in ongoing or planned trials that combine vaccines with other treatments or target earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vaccine therapy of prostate cancer]. Doehn, C., Böhmer, T., Sommerauer, M., et al.[2007]

Immunotherapy is emerging as a promising treatment for prostate cancer, which is traditionally treated with surgery, radiotherapy, and hormonal therapy, especially for advanced cases where docetaxel-based chemotherapy is FDA-approved and shows significant survival benefits.

Recent developments in prostate cancer immunotherapy, including dendritic cell vaccines and immune checkpoint inhibitors, have shown potential for targeted tumor destruction with less systemic toxicity, although these benefits are still being evaluated in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update: immunological strategies for prostate cancer. Drake, CG., Antonarakis, ES.[2021]

Sipuleucel-T, an FDA-approved dendritic-cell vaccine for prostate cancer, has shown a survival benefit of 4.1 months in patients with metastatic castration-resistant prostate cancer, highlighting its efficacy as a treatment option.

Combination therapies, particularly those involving prostate cancer vaccines and immune checkpoint inhibitors, show promise in enhancing treatment outcomes by boosting the immune response against tumors, with ongoing clinical studies exploring these strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining immunotherapies for the treatment of prostate cancer. Redman, JM., Gulley, JL., Madan, RA.[2020]

Sipuleucel-T is the first FDA-approved cancer vaccine for treating men with asymptomatic or minimally symptomatic castrate-resistant prostate cancer, marking a significant advancement in cancer immunotherapy.

The approval of Sipuleucel-T has sparked renewed interest in various vaccine approaches for prostate cancer, including viral vectors, dendritic cell vaccines, and DNA vaccines, each with unique benefits and challenges, and many are currently being tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on prostate cancer vaccines. Drake, CG.[2021]

Immunotherapy, particularly using the MVA-5T4 (TroVax(®)) vaccine, shows potential as a treatment for advanced castration-resistant prostate cancer, leveraging prostate-associated antigens for targeted therapy.

Preclinical studies and limited clinical trials indicate that the MVA-5T4 vaccine has demonstrated promise in treating prostate cancer, similar to its effectiveness observed in colorectal and renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on TroVax for the treatment of progressive castration-resistant prostate cancer. Abern, M., Kaufman, HL., Latchamsetty, K.[2021]

The vaccine-based immunotherapy regimen PF-06753512 (PrCa VBIR) demonstrated a safety profile similar to other immune checkpoint inhibitor (ICI) combination trials, with common side effects including fatigue and immune-related thyroid dysfunction in 70.3% of patients.

In patients with biochemical recurrence (BCR), 25.7% achieved a significant decline in PSA levels, indicating modest antitumor activity, while the treatment successfully stimulated antigen-specific immune responses across all patient cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Autio, KA., Higano, CS., Nordquist, L., et al.[2023]

In a study of 326 prostate adenocarcinoma patients from Spain and Norway, high expression of the immune checkpoint protein B7-H3 was linked to worse outcomes, including biochemical and clinical recurrence, indicating its potential as a target for immunotherapy.

Unlike B7-H3, PD-L1 expression did not show a correlation with clinical outcomes, suggesting that B7-H3 may be a more relevant biomarker for treatment strategies in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. Nunes-Xavier, CE., Kildal, W., Kleppe, A., et al.[2022]

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

Dendritic cell-based vaccines, such as sipuleucel-T, have been shown to be safe and effective in inducing immune responses in prostate cancer patients, leading to prolonged overall survival.

Sipuleucel-T, which uses patients' own immune cells loaded with tumor-associated antigens, received FDA approval in 2010, highlighting its significance as a treatment for metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell-based immunotherapy for prostate cancer. Jähnisch, H., Füssel, S., Kiessling, A., et al.[2022]

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]

Androgen suppression therapy (AST) is the standard treatment for metastatic prostate cancer (PCa), but patients often progress to metastatic castration-resistant prostate cancer (mCRPC), which has limited treatment options.

Current research is exploring various immunotherapy strategies, including combination therapies with chemotherapy and radiation, to overcome the immunosuppressive tumor microenvironment in mCRPC, showing promise in preclinical studies with new approaches like targeting the NKG2D pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, Current, and Future of Immunotherapies for Prostate Cancer. Boettcher, AN., Usman, A., Morgans, A., et al.[2020]

Citations

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Prostate cancer cells express more androgen receptor (AR ... The combination treatment with degarelix and pTVG-AR was found to delay tumor growth compared to treatment with degarelix and control vaccine ( ...

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

Key considerations for a prostate cancer mRNA vaccine The combination therapy demonstrated a clear survival benefit, with a three-year overall survival rate of 83 %, compared to 76 % in the ADT-alone group (HR for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04989946

Study Details | NCT04989946 | Androgen Deprivation, With ... To evaluate the safety of androgen deprivation and pTVG-AR DNA vaccine, alone or in combination with T-cell checkpoint blockade, in patients with newly ...

4. jitc.bmj.com jitc.bmj.com/content/12/5/e008848

Sequence of androgen receptor-targeted vaccination with ... We have also demonstrated that ADT combined with a DNA vaccine encoding the AR significantly slowed tumor growth and improved the survival of ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-09049

Degarelix with or without pTVG-AR and ... This trial aims to see whether giving degarelix alone or with pTVG-AR and nivolumb may work better in treating prostate cancer.

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Efficacy and safety of degarelix in patients with prostate cancer The data from the current study demonstrated that degarelix is non-inferior to goserelin in achieving and maintaining serum testosterone ...

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Cardiovascular Safety of Degarelix: Results From a 12-Month ... Treatment of men with prostate cancer using ADT has been associated with an increased risk of CV disease within months of commencing therapy. ADT is most ...

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A Study of Degarelix in Patients With Prostate Cancer The purpose of this study was to see if giving Degarelix every month for 7 months then stop treatment for 7 months (intermittent therapy) would show a ...