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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a combination of a new DNA vaccine, pTVG-HP, and the drug nivolumab (Opdivo) to determine if they can safely lower PSA levels in prostate cancer patients. It targets those who have undergone prostate surgery and have rising PSA levels, indicating cancer activity, without any spread to other parts of the body. Men who meet these criteria might be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that nivolumab is generally safe and well-tolerated in patients with various types of cancer. Studies have demonstrated a good safety record, with manageable side effects. Most side effects are mild to moderate, such as tiredness or a rash, though some patients may experience more serious side effects, which are less common.

For pTVG-HP, a DNA vaccine targeting prostate cancer, long-term studies have confirmed its safety. No major adverse events have been linked to this vaccine, with only mild side effects reported.

The combination of nivolumab with pTVG-HP has also undergone study. Research indicates this combination is safe, with no unexpected safety issues, suggesting that both treatments are tolerable for most patients.

Overall, the available data support the safety of both nivolumab and pTVG-HP for those considering joining this trial. However, discussing potential side effects with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pTVG-HP combined with Nivolumab for prostate cancer because it offers a novel approach that targets the immune system to fight cancer. Unlike traditional treatments like hormone therapy or chemotherapy, this combination utilizes Nivolumab, an immune checkpoint inhibitor, to boost the body's immune response by blocking PD-1 proteins on T-cells. Meanwhile, pTVG-HP is a DNA vaccine designed to stimulate a targeted attack on prostate cancer cells. This dual action not only enhances the immune system's ability to recognize and destroy cancer cells but also holds promise for better efficacy and potentially fewer side effects compared to standard treatments.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that nivolumab may effectively treat prostate cancer. In one study, 90.3% of patients who received nivolumab with radiotherapy did not experience cancer recurrence after two years, compared to the usual 75% in the past. Another study found that some patients experienced a drop in their prostate-specific antigen (PSA) levels, indicating cancer activity. In this trial, participants will receive both nivolumab and the pTVG-HP vaccine. The pTVG-HP vaccine targets a protein called prostatic acid phosphatase (PAP), often found in prostate cancer cells. While a complete drop in PSA levels was not observed, 21% of patients saw a noticeable decrease. Both treatments offer hope by potentially lowering PSA levels, which indicate prostate cancer activity. ^{6 7 8 9 10}

Who Is on the Research Team?

Hamid Emamekhoo, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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

I have previously received a DNA vaccine for prostate cancer.

My testosterone levels are below 50 ng/dL.

My cancer has spread to my bones or lymph nodes.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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Nivolumab in Patients with Metastatic Castration-Resistant ... Results: Among the 38 enrolled patients, DRD was identifiable in 30.5% (11/36) through ctDNA and/or whole-exome sequencing analyses. The overall ...

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Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows ... The overall safety profile was consistent with prior studies of Opdivo in combination with Yervoy with this dosing schedule. Grade three to five ...

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OPDIVO® (nivolumab) OPDIVO Qvantig™ is an FDA-approved alternative for most types of solid tumor cancer in adults that can be treated with OPDIVO® (nivolumab).†. Explore this ...

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Proof-of-principle Phase I results of combining nivolumab with ... Combination of nivolumab with ADT and HDR is well tolerated and associated with evidence of increased immune infiltration and antitumor ...

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