pTVG-HP + Nivolumab for Prostate Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Immunosuppressants, Corticosteroids, Androgens, others

Disqualifiers: Immunosuppression, HIV, Hepatitis, 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: 6

Duration: 48 weeks

19 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety of an investigational DNA vaccine, pTVG-HP, a plasmid DNA encoding human prostatic acid phosphatase (PAP), in combination with nivolumab, and the efficacy of this combination in decreasing serum Prostate-Specific Antigen (PSA) in patients with non-metastatic, non-castrate prostate cancer (clinical stage D0/M0).

Will I have to stop taking my current medications?

The trial requires that you stop taking medications or supplements with known hormonal effects, such as PC-SPES, megestrol acetate, finasteride, ketoconazole, estradiol, or Saw Palmetto. If you are taking other medications with possible anticancer effects, you must discuss them with the study doctor before joining the trial. Additionally, if you have used certain herbal supplements or experimental therapies for prostate cancer, you must stop them at least 4 weeks before starting the trial.

What data supports the effectiveness of the treatment pTVG-HP + Nivolumab for prostate cancer?

Research suggests that combining nivolumab with other drugs like ipilimumab has shown some effectiveness in treating certain types of prostate cancer, especially in patients with specific genetic mutations. However, the effectiveness of nivolumab alone or in combination with pTVG-HP for prostate cancer is not well-established, and more research is needed. ^{1 2 3 4 5}

Is the combination of pTVG-HP and Nivolumab safe for humans?

Nivolumab, used in various cancers, can cause immune-related side effects, which are reactions from the immune system that might affect different parts of the body. These side effects can be serious and include issues with blood cells, but they vary depending on the individual and the type of cancer being treated. ^{1 4 6 7 8}

What makes the pTVG-HP + Nivolumab treatment unique for prostate cancer?

The pTVG-HP + Nivolumab treatment is unique because it combines a DNA vaccine targeting a prostate-specific antigen with an immune checkpoint inhibitor, aiming to enhance the body's immune response against prostate cancer. This approach is different from standard treatments as it leverages the immune system to specifically target cancer cells, potentially offering a novel strategy for patients with advanced prostate cancer. ^{1 5 9 10 11}

Research Team

Hamid Emamekhoo, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

Men over 18 with non-metastatic, PSA-recurrent prostate cancer after surgery and possible radiation therapy. They should have a rising PSA level, be in good physical condition (ECOG score < 2), expect to live at least another year, and have normal blood counts and organ function. No recent immunosuppressants or other cancer treatments are allowed, except certain hormone therapies under specific conditions.

Inclusion Criteria

My blood, kidney, and liver tests are normal.

I am willing to give blood samples for research for up to a year after the study ends.

My prostate cancer has returned, is not spread, and my PSA levels are rising quickly.

Exclusion Criteria

My testosterone levels are below 50 ng/dL.

My cancer has spread to my bones or lymph nodes.

I have previously received a DNA vaccine for prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab and pTVG-HP with rhGM-CSF as an adjuvant if needed

48 weeks

Every two weeks for 6 visits, then every four weeks for 9 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for metastasis-free survival and PSA response

Up to 5 years

Treatment Details

Interventions

• Nivolumab
• pTVG-HP

Trial Overview The trial is testing the safety of pTVG-HP, a DNA vaccine targeting prostate acid phosphatase (PAP), combined with Nivolumab, an immune checkpoint inhibitor. The goal is to see if this combination can lower serum Prostate-Specific Antigen (PSA) levels in patients whose prostate cancer has returned but hasn't spread.

Participant Groups

Group I: Treatment Group Experimental Treatment 3 Interventions

* Nivolumab 240 mg IV every two weeks x 6 beginning day 1, then every four weeks x 9 beginning week 12 * pTVG-HP (100 µg) administered intradermally (i.d.) every two weeks x 6 beginning day 1, then every four weeks x 9 beginning week 12 * rhGM-CSF (208 µg) administered intradermally (i.d.) every two weeks x 4 beginning week 4, then every four weeks x 9 beginning week 12 NOTE: Only administered to patients for whom serum PSA obtained week 4 \> serum PSA obtained at day 1.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Madison Vaccines Inc. (MVI)

Collaborator

Trials

1

Recruited

20+

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

AIQ Solutions

Industry Sponsor

Trials

3

Recruited

80+

AIQ Solutions

Collaborator

Trials

1

Recruited

20+

Findings from Research

Prostate cancer has a challenging immunosuppressive environment, making it difficult to treat with traditional immunotherapy; currently, sipuleucel-T is the only FDA-approved immunotherapy specifically for prostate cancer, effective mainly for select patients with indolent metastatic castration-resistant prostate cancer.

Future strategies in immuno-oncology for prostate cancer may involve innovative approaches like bispecific antibodies and CAR-T cells targeting specific markers on tumor cells, which could improve patient outcomes by overcoming the immune barriers present in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. Wong, RL., Yu, EY.[2022]

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]

In a phase-2 trial involving 15 metastatic prostate cancer patients with AR-V7-expressing tumors, the combination of nivolumab and ipilimumab showed promising efficacy, particularly in patients with DNA-repair deficiency (DRD) mutations, where PSA response rates were higher (33% vs. 0% in DRD-negative tumors).

The study found that patients with DRD-positive tumors had significantly better progression-free survival (PFS) and overall survival (OS) compared to those without DRD mutations, indicating that targeting this specific tumor profile may enhance treatment outcomes without introducing new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Boudadi, K., Suzman, DL., Anagnostou, V., et al.[2023]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

Nivolumab is a PD-1 immune checkpoint inhibitor that effectively enhances antitumor immunity by blocking the PD-1 receptor on activated T cells, which helps reverse immune suppression in cancer patients.

Clinical trials have demonstrated the efficacy of nivolumab in treating various cancers, including non-small-cell lung cancer, melanoma, and renal cell carcinoma, making it a promising option in targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. Guo, L., Zhang, H., Chen, B.[2022]

References

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

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

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

Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. [2022]

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

Anti-PD-1-CTLA4 Combo Hits 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. United States pubmed.ncbi.nlm.nih.gov

Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. [2023]

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

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]

7. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

9. Australia pubmed.ncbi.nlm.nih.gov

The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine. [2019]

11. Australia pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. [2022]