ADXS-504 Immunotherapy for Prostate Cancer

Overseen By Mark N. Stein, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Mark Stein

Must not be taking: LHRH agonists, Antiandrogens

Disqualifiers: Metastatic disease, Brain metastasis, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary Objective: - To evaluate the safety and tolerability of ADXS-504 and to determine the MTD (maximum tolerated dose) or RP2D (recommended phase two dose) Secondary Objectives: * To characterize the immunological activity of ADXS-504, administered as; and to characterize the genomic profiles of study subjects * To evaluate the effects of ADXS-504 on change in PSA * To evaluate time to PSA progression

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. Specifically, you must not have used LHRH agonists or antagonists within 6 months, oral antiandrogens within 3 months, or certain other agents like 5 alpha reductase inhibitors and systemic steroids within the past month.

What data supports the effectiveness of the treatment ADXS-504 for prostate cancer?

Research suggests that immunotherapy, like ADXS-504, can boost the immune system to slow down tumor growth in prostate cancer. Preliminary data from trials combining immunotherapy with other treatments show promise, especially in patients with less aggressive forms of the disease. ^{1 2 3 4 5}

Is ADXS-504 immunotherapy safe for humans?

Immunotherapy treatments for prostate cancer, including those similar to ADXS-504, have generally shown minimal toxicity in early clinical trials, suggesting they are relatively safe for humans. Common side effects reported in similar treatments include fatigue, diarrhea, and infusion reactions, but these are typically not severe. ^{6 7 8 9 10}

How is the treatment ADXS-504 different from other prostate cancer treatments?

ADXS-504 is a novel immunotherapy for prostate cancer that aims to enhance the body's immune response against cancer cells, which is different from traditional treatments like hormone therapy or chemotherapy. Unlike these standard treatments, ADXS-504 specifically targets the immune system to recognize and attack prostate cancer cells, potentially offering a new option for patients with tumors that are less responsive to conventional therapies. ^{1 4 11 12 13}

Research Team

Mark N. Stein

Principal Investigator

Columbia University

Eligibility Criteria

Men over 18 with recurrent prostate cancer after primary therapy like surgery or radiation, not on active treatment for other cancers. They must have a stable performance status, adequate organ function, and rising PSA levels according to specific criteria. Participants need to provide consent and health information release, agree to contraceptive guidance if applicable, and cannot have brain metastases or severe autoimmune diseases.

Inclusion Criteria

I had initial treatment for prostate cancer and any follow-up treatment was over 6 months ago.

I am 18 years old or older.

I am a man and will use birth control during and for 4 months after treatment.

Exclusion Criteria

Known allergy to study formulation components

History of listeriosis

Implanted medical device posing high risk for bacterial colonization

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADXS-504 monotherapy with dose escalation to evaluate safety and tolerability

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ADXS-504

Trial Overview The trial is testing ADXS-504 immunotherapy in men with recurring prostate cancer. It aims to find the safest dose that patients can tolerate (MTD) or recommend for future studies (RP2D), measure immune response effects of the drug, observe changes in PSA levels, and assess time until PSA levels rise again.

Participant Groups

Group I: ADXS-504 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Subjects with Biochemically Recurrent Prostate Cancer will receive ADXS-504 with dose escalation schema.

Who Is Running the Clinical Trial?

Mark Stein

Lead Sponsor

Trials

4

Recruited

150+

Findings from Research

Immunotherapy is becoming a promising treatment option for prostate cancer, with ongoing phase III trials exploring various vaccine and immune-based therapies that enhance immune responses and slow tumor growth.

Current evidence suggests that patients with less aggressive forms of prostate cancer may benefit more from immunotherapies, and ongoing trials are investigating combinations of these therapies with traditional treatments to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Immunotherapies in Prostate Cancer. Strauss, J., Madan, RA.[2022]

Prostate cancer, once metastatic, is currently treated with a standard regimen of docetaxel and prednisone, but there is growing interest in immunotherapy options, including vaccines and monoclonal antibodies, which may enhance treatment effectiveness.

Recent phase III clinical trials suggest a need to change how we measure the success of immunotherapy, advocating for overall survival and immune response as key endpoints instead of just tumor size, which may not accurately reflect patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in prostate cancer: review of the current evidence. Fernández-García, EM., Vera-Badillo, FE., Perez-Valderrama, B., et al.[2022]

Therapeutic cancer vaccines, including those beyond sipuleucel-T, are showing promise as effective treatments for prostate cancer, particularly in patients with earlier and less aggressive stages of the disease.

Combining these vaccines with traditional prostate cancer treatments and immune checkpoint inhibitors is currently being explored in clinical trials, with preliminary results indicating potential for enhanced immune responses and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic vaccines for prostate cancer: recent advances and future directions. Strauss, J., Madan, RA.[2018]

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]

Docetaxel is currently the only treatment that significantly prolongs survival for men with hormone-refractory prostate cancer, highlighting the limited options available.

Prostate cancer may be a promising target for immunotherapy, but due to the tumor's ability to evade the immune system, effective treatment will likely require a combination of different immunotherapies or a mix of immunotherapy with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current immunotherapeutic strategies in prostate cancer. Grosso, JF., Drake, CG.[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]

Immune checkpoint inhibitors (ICIs) show a median overall survival of 14.1 months in prostate cancer patients, with anti-CTLA-4 monotherapy providing the longest survival at 24.9 months, while anti-PD-1/PD-L1 combined with anti-CTLA-4 resulted in the shortest at 9.2 months.

The anti-PD-1/PD-L1 monotherapy group had the lowest incidence of adverse events, while common side effects from ICI monotherapy included fatigue, diarrhea, and infusion reactions, highlighting the need for further research on combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis. Noori, M., Azizi, S., Mahjoubfar, A., et al.[2023]

Immunotherapy has shown promise in treating various cancers, but prostate cancer has lagged behind, with only one FDA-approved agent (sipuleucel-T) and limited success in improving survival rates for advanced cases.

Recent advancements in immunotherapy strategies, including targeting T cells and modifying the tumor microenvironment, suggest that there is potential for improved outcomes in prostate cancer, especially as new combinations of therapies are being tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for prostate cancer: False promises or true hope? Rekoske, BT., McNeel, DG.[2018]

Sipuleucel-T is the only prostate cancer vaccine that has completed Phase III trials and received FDA approval, targeting the prostatic acid phosphatase antigen to stimulate an immune response against prostate cancer.

Current research includes ongoing trials for other vaccines like Prostvac-TRICOM and Ad5-prostate-specific antigen, highlighting the need to overcome immune regulatory challenges to enhance the effectiveness of these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer vaccines in clinical trials. Lubaroff, DM.[2020]

Immunotherapy shows promise as a new treatment option for metastatic prostate cancer, potentially delaying disease progression with minimal toxicity compared to traditional therapies like chemotherapy and androgen-deprivation therapy.

Current phase III clinical trials are exploring various immunotherapy strategies, including immune-modulating agents and combination therapies, indicating a growing interest in developing safer and more effective treatments for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for prostate cancer - recent progress in clinical trials. Kipp, RT., McNeel, DG.[2007]

Androgen deprivation therapy (ADT) not only reduces testosterone levels but also increases androgen receptor (AR) expression in prostate cancer cells, which can enhance the immune system's ability to recognize and attack these cancer cells.

Combining ADT with a DNA vaccine targeting the AR significantly improved antitumor responses in mouse models, suggesting that this strategy may effectively overcome resistance mechanisms associated with AR overexpression in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. Olson, BM., Gamat, M., Seliski, J., et al.[2018]

The study identified EP4 as a key target for immunotherapy in prostate cancer, showing that the novel EP4 antagonist YY001 can enhance T cell activity while inhibiting immunosuppressive myeloid-derived suppressor cells (MDSCs).

Combining YY001 with anti-PD-1 antibodies resulted in a strong antitumor immune response, converting previously unresponsive prostate cancers into responsive ones, leading to significant tumor regression and improved long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy. Peng, S., Hu, P., Xiao, YT., et al.[2022]

Immunotherapy, particularly with the FDA-approved sipuleucel-T, has emerged as a promising treatment option for metastatic castrate-resistant prostate cancer (CRPC), complementing traditional therapies like androgen deprivation and chemotherapy.

Current clinical trials are exploring various immunotherapy approaches, including cancer vaccines and immune checkpoint inhibitors, to enhance treatment effectiveness and potentially improve patient outcomes in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: immunotherapy for prostate cancer. Tse, BW., Jovanovic, L., Nelson, CC., et al.[2021]

References

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

Integrating Immunotherapies in Prostate Cancer. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Immunotherapy in prostate cancer: review of the current evidence. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Therapeutic vaccines for prostate cancer: recent advances and future directions. [2018]

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

Current immunotherapeutic strategies in prostate cancer. [2007]

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

Update: immunological strategies for prostate cancer. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis. [2023]

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

Immunotherapy for prostate cancer: False promises or true hope? [2018]

9. England pubmed.ncbi.nlm.nih.gov

Prostate cancer vaccines in clinical trials. [2020]

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

Immunotherapy for prostate cancer - recent progress in clinical trials. [2007]

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

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. [2018]

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

Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy. [2022]

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

From bench to bedside: immunotherapy for prostate cancer. [2021]