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

Trial Summary

What is the purpose of this trial?

The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.

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.

What data supports the effectiveness of the treatment involving Degarelix, Firmagon, Nivolumab, Opdivo, pTVG-AR, pTVG-AR, MVI-118 for prostate cancer?

Research suggests that combining immune checkpoint inhibitors like Nivolumab with tumor vaccines may enhance the immune response in prostate cancer, potentially leading to better outcomes. Although specific data on this combination is limited, similar approaches have shown promise in other cancers. ^{1 2 3 4 5}

Is the combination of vaccine and Nivolumab safe for prostate cancer treatment?

The research suggests that immunotherapy for prostate cancer, including vaccines and immune checkpoint inhibitors like Nivolumab, has shown potential benefits with targeted tumor destruction and minimal systemic toxicity. However, the full safety profile in humans is still being evaluated, and combination therapies are being explored to improve outcomes. ^{2 3 6 7 8}

How is the treatment with Degarelix and Nivolumab unique for prostate cancer?

This treatment is unique because it combines a vaccine with Nivolumab, an immune checkpoint inhibitor, which may enhance the immune system's ability to fight prostate cancer. This combination approach is novel as it aims to improve outcomes by potentially creating and recruiting tumor-specific T cells to the tumor, increasing their effectiveness. ^{3 8 9 10 11}

Research Team

Christos Kyriakopoulos, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

An update on TroVax for the treatment of progressive castration-resistant prostate cancer. [2021]

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

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Past, Current, and Future of Immunotherapies for Prostate Cancer. [2020]

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

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. [2022]

5. 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]

6. England 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). [2023]

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

Update: immunological strategies for prostate cancer. [2021]

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

Combining immunotherapies for the treatment of prostate cancer. [2020]

9. Egypt pubmed.ncbi.nlm.nih.gov

Dendritic cell-based immunotherapy for prostate cancer. [2022]

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

Update on prostate cancer vaccines. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Vaccine therapy of prostate cancer]. [2007]