Cancer Vaccine for Prostate Cancer

(PGV-Prostate Trial)

Overseen By Monali Fatterpekar

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Ashutosh Kumar Tewari

Must be taking: Anti-androgens

Must not be taking: Immunosuppressants

Disqualifiers: Metastatic disease, HIV/AIDS, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 37 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new personalized cancer vaccine combined with other treatments to determine their safety and tolerability for individuals with a history of aggressive prostate cancer. It targets those who have undergone surgery and other standard treatments but remain tumor-free, though they may still exhibit signs of prostate cancer, such as a persistent or rising PSA (a protein indicating cancer activity). Participants must have completed surgery and other standard treatments and be able to provide a tissue sample for genetic testing. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial allows participants to continue hormonal therapy (like anti-androgens) during the study. However, the protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

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

Studies have shown that the PGV-001 vaccine, when combined with Poly-ICLC, is safe and generally well-tolerated, enhancing the body's immune response without serious side effects. Research indicates that adding CDX-301 to PGV-001 and Poly-ICLC remains safe, with only a slight increase in side effects. This suggests the treatment doesn't cause significantly more harm than using just one component. Ongoing research ensures its safety for individuals with a history of aggressive prostate cancer. As a Phase 1 study, this marks the first time the treatment is tested in humans, focusing primarily on safety and how well the body tolerates it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they harness a personalized genomic vaccine (PGV-001) to tailor the therapy to each patient's genetic makeup. Unlike standard treatments such as hormone therapy or chemotherapy, this approach aims to activate the patient's immune system to specifically target cancer cells. Additionally, combining PGV-001 with Poly-ICLC and CDX-301 could enhance the immune response, potentially offering a more precise and effective treatment option. This innovative strategy represents a shift from traditional treatments, potentially reducing side effects and improving patient outcomes by focusing on personalized, immune-based therapies.

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

Research shows that the PGV-001 vaccine can help the body's immune system fight prostate cancer. Patients who received the vaccine had more immune cells that attack cancer. In this trial, participants in Cohort 1 will receive the PGV-001 vaccine and Poly-ICLC. Studies have shown that Poly-ICLC activates the immune system and shrinks tumors in prostate cancer patients. Participants in Cohort 2 will receive the PGV-001 vaccine, Poly-ICLC, and CDX-301. CDX-301 supports the immune system, and its use with other treatments has led to successful results in studies. Together, these treatments aim to use the immune system to find and destroy cancer cells effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Ashutosh Tewari, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Sujit S Nair, Ph.D.

Principal Investigator

Icahn School of Medicine at Mount Sinai

Dara Lundon, MD MSc MBA PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for men over 18 with a history of aggressive prostate cancer who are currently tumor-free. They must have completed all standard treatments, including surgery and chemotherapy, and not be on any immune-suppressing drugs. Participants need good blood counts and organ function, agree to use contraception if necessary, and provide tissue samples for sequencing.

Inclusion Criteria

I have had surgery to remove my prostate and am currently cancer-free according to imaging tests.

It has been over 4 weeks since I had general anesthesia and over 72 hours since any local or epidural anesthesia.

The subject must have at the time of screening acceptable hematologic, hepatic, and renal function, defined by the following: Absolute neutrophil count > 1000/mm3, Platelet count > 50,000/mm3, Creatinine < 2.5 mg/dl, Total bilirubin ≤ 1.5 mg/dl, (except in patients with gilbert syndrome who can have total bilirubin < 3.0 mg/dl), Transaminases < 2 times above the upper limits of the institutional normal. INR<2 if off of anticoagulation. Patients on anticoagulation therapy with an INR>2 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage. Adequate venous access (for leukapheresis and blood draws).

Exclusion Criteria

I am under 18 years old or cannot give consent.

The subject has a history of anaphylaxis or other serious adverse reactions relating to administration of any components of the investigational product.

My biopsy from another facility is not good enough for further tests, and I don't want another biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PGV001-based personalized multi-peptide vaccines in combination with CDX-301

37 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

Long-term follow-up

Participants are monitored for radiographic free survival

10 years

What Are the Treatments Tested in This Trial?

Interventions

• CDX-301
• PGV-001
• Poly-ICLC

Trial Overview The study tests the safety of PGV001-based personalized multi-peptide vaccines combined with CDX-301 in patients who've had aggressive prostate cancer but are now tumor-free. It's designed to see how well they tolerate this new treatment approach after their standard care.

How Is the Trial Designed?

Group I: Cohort 3 - Expansion treatment cohort Experimental Treatment 3 Interventions

An expansion cohort if the treatment of all 3 together has not triggered a safety stopping event.

Group II: Cohort 2 - Secondary treatment cohort Experimental Treatment 3 Interventions

Patients receive the personalized genomic vaccine (PGV) and Poly-ICLC, and CDX-301

Group III: Cohort 1 - Primary treatment cohort Experimental Treatment 2 Interventions

Patients receive the personalized genomic vaccine (PGV) and Poly-ICLC.

Who Is Running the Clinical Trial?

Ashutosh Kumar Tewari

Lead Sponsor

Trials

3

Recruited

150+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11119780/

Innovative Drug Modalities for the Treatment of Advanced ... Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03835533

NCT03835533 | Platform Study for Prostate Researching ... ≥ 50% reduction in Prostate-Specific Antigen (PSA) from baseline, with a repeat assessment confirming the results at least 3 weeks later;

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11995007/

Clinical and Translational Results from PORTER, a ... Cohort C. CDX-301 was administered at 75 μg/kg s.c. once daily on immune-priming lead-in days 1 to 5 and 22 to 26 (10 total doses).

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/33/NCT03835533/Prot_002.pdf

PORTER Appendix Cohort C - Parker Institute for Cancer ... These observations suggest that combination of CDX-301 with immunotherapies generating effective CD8 T cell responses, such as INO-5151, may lead to an ...

5. reports.mountsinai.org reports.mountsinai.org/article/uro2022-06-new-clinical-trial-exploring-personalized-vaccine

New Clinical Trial Exploring Personalized Vaccine for ... “Personalized vaccine therapy has been studied and has been found to be very safe and effective in achieving tumor regression in other cancers, but this ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05010200

The Safety and Tolerability of PGV001-based Personalized ... This proof of concept study is designed to test the safety and tolerability of PGV001-based personalized multi-peptide vaccines in combination with CDX-301 ...

7. aacrjournals.org aacrjournals.org/cancerdiscovery/article/15/5/930/761991/PGV001-a-Multi-Peptide-Personalized-Neoantigen

PGV001, a Multi-Peptide Personalized Neoantigen Vaccine ... Our results indicate that the peptide and poly-ICLC vaccine platform is safe, feasible, and capable of inducing enduring T-cell and B-cell immunity in all ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04136

A Vaccine (PGV001) in Combination with Immunotherapy ... Giving PGV001, CDX-301 and poly-ICLC may help the immune system identify prostate cancer as an illness and attack it. Eligibility Criteria ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8193725/

Safety and Efficacy of Personalized Cancer Vaccines in ... Growing studies show that the combination can elevate the antitumor efficacy with acceptable safety and minimal additional toxicity compared with single agent ...

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

Key considerations for a prostate cancer mRNA vaccine In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens ( ...