CAR T Cells for Prostate Cancer

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Pennsylvania

Must be taking: GnRH therapy

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Active infections, Cardiovascular disability, Autoimmune diseases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients requiring chronic treatment with systemic steroids or immunosuppressant medications are excluded. Low-dose corticosteroids equivalent to prednisone 10 mg/day or lower are acceptable.

What data supports the effectiveness of the treatment TmPSMA-02 for prostate cancer?

Research shows that CAR T cells targeting PSMA (a protein found in prostate cancer cells) can effectively reduce tumor size and improve survival in animal models. Additionally, these cells have been shown to specifically attack prostate cancer cells without harming healthy cells, indicating potential effectiveness in treating prostate cancer. ^{1 2 3 4 5}

Is the CAR T cell treatment for prostate cancer safe for humans?

Research indicates that PSMA-targeting CAR T cells, including those with a dominant-negative TGFβ receptor, have shown safety and feasibility in prostate cancer treatment. ^{1 2 3 4 5}

How is the treatment TmPSMA-02 different from other prostate cancer treatments?

TmPSMA-02 is a unique treatment for prostate cancer because it uses genetically modified T cells that target the prostate-specific membrane antigen (PSMA) and include a dominant-negative TGFβ receptor, which helps the T cells function better in the tumor environment. This approach is novel as it combines multiple genetic modifications to enhance the effectiveness of CAR T cell therapy specifically for solid tumors like prostate cancer. ^{1 2 3 4 6}

Research Team

Eligibility Criteria

This trial is for adults over 18 with advanced prostate cancer that's resistant to hormone therapy. They must have tried at least one standard treatment, including androgen receptor inhibitors or taxane-based chemo. Participants need normal liver function, kidney function (not on dialysis), and a healthy heart with an ejection fraction of at least 45%.

Inclusion Criteria

I have had treatment for advanced prostate cancer, including hormone therapy or chemotherapy.

My kidney function is good and I am not on dialysis.

I have little to no trouble breathing and my oxygen level is above 92% without assistance.

Exclusion Criteria

I have had T-cell therapy before, but not Sipuleucel-T.

I am on strong medication for an autoimmune disease, but I don't have MS.

I do not have any active, uncontrolled infections.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TmPSMA-02 CAR T cells at various dose levels following lymphodepletion with fludarabine and cyclophosphamide

Dose escalation phase with multiple levels

Multiple visits for dose administration and monitoring

Retreatment

Subjects who have demonstrated clinical benefit may receive retreatment with TmPSMA-02 CAR T cells

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• TmPSMA-02 (CAR T-cell Therapy)

Trial Overview The study tests different doses of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer. It's an early-phase trial to see if the treatment is safe, tolerable, can be made reliably, and works against this type of cancer using a step-by-step dose increase method.

Participant Groups

Group I: Dose Level 3 Experimental Treatment 1 Intervention

After lymphodepleting chemotherapy subjects to receive 3x10(8) TmPSMA-02 CAR T Cells

Group II: Dose Level 2 Experimental Treatment 1 Intervention

After lymphodepleting chemotherapy subjects to receive 1x10(8) TmPSMA-02 CAR T Cells

Group III: Dose Level 1 Experimental Treatment 1 Intervention

After lymphodepleting chemotherapy subjects to receive 5 x10(7) TmPSMA-02 CAR T Cells

Group IV: Dose Level -1 Experimental Treatment 1 Intervention

After lymphodepleting chemotherapy subjects to receive 1x10(7) TmPSMA-02 CAR T Cells

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Tceleron Therapeutics, Inc.

Industry Sponsor

Trials

3

Recruited

40+

Prostate Cancer Foundation *PCF)

Collaborator

Trials

1

Recruited

20+

Findings from Research

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]

A novel CAR T cell therapy targeting a new epitope in the prostate-specific membrane antigen (PSMA) showed promising results in eradicating established prostate cancer in a preclinical mouse model.

Combining the PSMA CAR T cells with low-dose docetaxel chemotherapy significantly enhanced tumor growth inhibition, suggesting that this combination could be an effective treatment strategy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. Alzubi, J., Dettmer-Monaco, V., Kuehle, J., et al.[2020]

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]

Chimeric antigen receptor (CAR) T cells targeting prostate-specific membrane antigen (PSMA) effectively eliminate prostate cancer in various animal models, demonstrating strong antitumor activity and specificity.

The success of these PSMA-targeted T cells in eradicating tumors is linked to their survival in the body for at least one week, suggesting that long-term persistence is crucial for achieving durable remissions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Gade, TP., Hassen, W., Santos, E., et al.[2018]

A third-generation Chimeric Antigen Receptor (CAR) targeting Prostate Specific Membrane Antigen (PSMA) was developed to enhance the efficacy of CAR-T cell therapy for metastatic prostate cancer, but it showed similar in vitro antitumor activity to a second-generation CAR with only one costimulatory domain.

The addition of a second costimulatory domain in the third-generation CAR led to increased activation-induced cell death and an exhausted phenotype in CAR-T cells, suggesting that more costimulatory signals may not always improve treatment outcomes and should be carefully evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Specific CAR-Engineered T Cells for Prostate Cancer: CD28 Outperforms Combined CD28-4-1BB "Super-Stimulation". Zuccolotto, G., Penna, A., Fracasso, G., et al.[2021]

The study developed an inverted chimeric cytokine receptor (ICR) to enhance the effectiveness of CAR-T cells targeting prostate cancer, showing significant improvements in anti-tumor capabilities in both in vitro and in vivo models.

PSMA-CAR-T cells co-expressing ICR not only demonstrated superior anti-tumor activity but also prolonged survival in mouse models, suggesting a promising new therapeutic strategy for treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric cytokine receptor enhancing PSMA-CAR-T cell-mediated prostate cancer regression. Weimin, S., Abula, A., Qianghong, D., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. [2021]

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

PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. [2020]

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

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

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

Targeted elimination of prostate cancer by genetically directed human T lymphocytes. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

PSMA-Specific CAR-Engineered T Cells for Prostate Cancer: CD28 Outperforms Combined CD28-4-1BB "Super-Stimulation". [2021]

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

Chimeric cytokine receptor enhancing PSMA-CAR-T cell-mediated prostate cancer regression. [2021]