CAR T Cell Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: LHRH agonist/antagonist

Disqualifiers: Arrhythmia, Optic neuritis, Stroke, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for prostate cancer that no longer responds to traditional hormone therapy and has metastasized. The treatment uses specially engineered immune cells, called PSCA-CAR T cells, designed to target and kill cancer cells. The main goal is to determine the optimal dose and understand any side effects. Men with prostate cancer that persists despite hormone treatment and has progressed with other therapies might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior chemotherapy is allowed if at least 2 weeks have passed before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that PSCA-CAR T cells are likely to be safe for humans?

Research has shown that PSCA-CAR T cells, a treatment where immune cells are modified to attack cancer cells, have been tested for safety in people with advanced prostate cancer. In earlier studies, some patients experienced side effects like bladder inflammation, but these were manageable. The studies also suggest that this treatment might help fight cancer.

This trial is in its early stages, so researchers are primarily focused on ensuring the treatment's safety and determining the right dose. Early trials like this are crucial for understanding how well people can tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PSCA-CAR T cell therapy for prostate cancer because it offers a groundbreaking approach that differs from traditional treatments like hormone therapy, chemotherapy, or radiation. Unlike these standard options, which often target cancer cells indirectly, PSCA-CAR T cells are engineered to directly attack cancer cells by recognizing a specific protein, PSCA, found on their surface. This direct targeting mechanism could lead to more precise and effective destruction of cancer cells. Additionally, this therapy uses the patient's own modified T cells, potentially reducing the risk of severe side effects associated with other systemic treatments.

What evidence suggests that PSCA-CAR T cells might be an effective treatment for prostate cancer?

Research has shown that PSCA-CAR T cell therapy could be a promising treatment for advanced prostate cancer that has spread and resists standard hormone therapy. Studies have found that these specially designed immune cells can effectively locate and attack prostate cancer cells. Early results from clinical trials suggest that this treatment might slow cancer growth in patients with this severe form of prostate cancer. Some patients have experienced significant improvements, highlighting the therapy's potential. However, this treatment is still under study in this trial to ensure its effectiveness and safety. ^{1 2 6 7 8}

Who Is on the Research Team?

Tanya B Dorff

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that's resistant to hormone therapy and has spread, who are fit enough for treatment (ECOG 0-2), have PSCA+ tumors, and can consent. They must not have certain central nervous system conditions, uncontrolled infections, HIV/hepatitis B/C, bleeding disorders or recent strokes. Participants need proper liver/kidney function and agree to birth control during the study.

Inclusion Criteria

All participants must have the ability to understand and the willingness to sign a written informed consent

Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

Documented PSCA+ tumor expression as evaluated by City of Hope (COH) Pathology Care

Exclusion Criteria

You have a history of optic neuritis or other immune or inflammatory diseases that affect the brain and spinal cord, including seizures.

You have a known bleeding disorder like von Willebrand's disease or hemophilia.

You have had a stroke or bleeding in the brain within the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients may receive a lymphodepleting regimen including fludarabine and cyclophosphamide intravenously

3-5 days

Daily visits for lymphodepletion

Treatment

Patients receive autologous anti-PSCA-CAR T lymphocytes intravenously

1 day

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Day 1, every 2 days for up to 14 days, weekly for up to 1 month, every month for up to 1 year, and then annually

What Are the Treatments Tested in This Trial?

Interventions

• PSCA-CAR T Cells

Trial Overview

The trial is testing a new type of immune cell therapy called PSCA-CAR T cells on men with metastatic castration-resistant prostate cancer. These cells are genetically modified to attack prostate cancer cells by recognizing a specific antigen present on their surface.

How Is the Trial Designed?

Group I: Treatment (PSCA CAR T cells) Experimental Treatment 4 Interventions

Patients may receive lymphodepleting regimen (either standard or modified) including fludarabine IV on days -5 to -3 and cyclophosphamide IV on days -5 to -3 or on days -4 and/or -3. The study PI and the protocol team will choose a chemotherapy regimen, for lymphodepletion prior to the PSCA-CAR T cell infusion (with the exception of cohorts 1 and -1 which will not receive lymphodepletion), based on the research participant's disease type and prior therapies. Patients then receive autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A new chimeric T-cell receptor (TCR) targeting the prostate stem cell antigen (PSCA) was successfully developed, showing promise for treating prostate cancer by activating cytotoxic T-cells against PSCA-positive tumor cells.

This innovative approach involves genetic engineering of T-cells to enhance their ability to recognize and attack prostate cancer cells, potentially offering a new immunotherapeutic strategy for patients with minimal residual disease or advanced tumor stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells. Morgenroth, A., Cartellieri, M., Schmitz, M., et al.[2021]

The study demonstrates that PSMA-targeting CAR T cells, which are engineered to include a dominant-negative TGFβ receptor, are safe and feasible for use in treating prostate cancer.

This approach suggests a promising strategy for enhancing the effectiveness of CAR T cell therapy in prostate cancer patients, potentially improving their treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells with a Dominant-Negative TGFβ Receptor Are Safe and Feasible. [2022]

The study developed a third-generation CAR T cell targeting the prostate stem cell antigen (PSCA), which showed specific immune responses and effective tumor cell killing in laboratory tests.

In mouse models, treatment with PSCA-CAR T cells significantly delayed tumor growth and improved survival, suggesting potential for this therapy in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. Hillerdal, V., Ramachandran, M., Leja, J., et al.[2021]

Engineering NK-92 cells with a CAR that targets the prostate-specific membrane antigen (PSMA) allows these cells to effectively kill prostate cancer cells while sparing healthy cells, demonstrating strong potential for targeted therapy.

In mouse models, irradiated NK-92/CAR cells not only inhibited tumor growth but also improved survival rates, suggesting that this approach could be a promising and safe immunotherapy for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. Montagner, IM., Penna, A., Fracasso, G., et al.[2021]

Citations

1.

nature.com

nature.com/articles/s41591-024-02979-8

PSCA-CAR T cell therapy in metastatic castration-resistant ...

This study validates PSCA as a viable CAR T cell therapeutic target and provides encouraging early clinical data to support further studies, ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5019

Final results from phase I study of PSCA-targeted chimeric ...

Conclusions: PSCA-CAR T cells have anti-cancer activity in mCRPC with DLT of cystitis. LD was required for greater expansion and activity; lower ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05805371

NCT05805371 | PSCA-Targeting CAR-T Cells Plus or ...

This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor (CAR)-4-1BB/ ...

4.

cityofhope.org

cityofhope.org/study-car-t-for-prostate-cancer-shows-efficacy

Study: CAR T for Prostate Cancer Shows Efficacy

The trial's preliminary major finding is that PSCA-directed CAR T cells may be effective against mCRPC, the research team said. This opens up ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39737899/

PSCA-targeted BPX-601 CAR T cells with pharmacological ...

These results suggest that pharmacological activation of GoCAR-T® cells is feasible and may offer a promising avenue to control chimeric antigen ...

6.

urotoday.com

urotoday.com/conference-highlights/asco-2023/asco-2023-prostate-cancer/144897-asco-2023-5019-final-results-from-phase-i-study-of-psca-targeted-chimeric-antigen-receptor-car-t-cells-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc.html

Final Results from Phase I Study of PSCA-Targeted CAR T ...

Based on this data, Dr. Dorff and colleagues report that PSCA-CAR T cells have anti-cancer activity in mCRPC with DLT of cystitis. PSCA is rest ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5112

A phase 1b study of PSCA CAR T cells plus or minus ...

We previously demonstrated initial safety of a PSCA CAR T cells in patients with mCRPC following a reduced lymphodepletion regimen (LD) in a ...

8.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02186

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for ...

This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor (CAR)-4-1BB/ ...