CAR T Cells for Prostate Cancer

Overseen By Abramson Cancer Center Clinical Trials Service

Age: 18+

Sex: Male

Trial Phase: Phase 1

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

Compensation: Varies

Number of Visits: Unknown

Duration: Dose escalation phase with multiple levels

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called TmPSMA-02, a type of CAR T-cell therapy, for prostate cancer that has spread and is unresponsive to hormone therapy. The main goal is to determine the treatment's safety and effectiveness. Participants will receive varying doses to identify the optimal amount. The trial seeks men whose cancer has progressed despite previous treatments and who maintain low testosterone levels. As a Phase 1 trial, this research aims to understand how the treatment functions in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that TmPSMA-02 CAR T cells are likely to be safe for humans?

Research shows that TmPSMA-02 CAR T cells could aid in treating prostate cancer. In earlier studies, these specially designed immune cells were tested on prostate cancer patients. The results suggested that the treatment was generally well-tolerated.

Some patients experienced side effects, but these were mostly manageable. The studies did not report any severe unexpected reactions. As this is a Phase 1 trial, the main focus is on safety. Researchers are carefully increasing doses to determine the safest and most effective amount.

In summary, while early results are promising and indicate the treatment is well-tolerated, this trial will gather more safety data to ensure it is safe for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TmPSMA-02 because it represents a novel approach to treating prostate cancer using CAR T cells. Unlike traditional treatments like hormone therapy, chemotherapy, or radiation, which target cancer cells broadly, TmPSMA-02 specifically targets prostate-specific membrane antigen (PSMA) on cancer cells. This precision could lead to more effective cancer cell destruction with potentially fewer side effects. Additionally, the varying doses of TmPSMA-02 being tested aim to optimize the treatment's effectiveness and safety, which could pave the way for more personalized cancer care.

What evidence suggests that TmPSMA-02 CAR T cells might be an effective treatment for prostate cancer?

Research shows that TmPSMA-02 CAR T cells target a protein called PSMA, often found in high amounts on prostate cancer cells, making PSMA an ideal treatment target. Early studies have demonstrated that CAR T cells can effectively locate and destroy these cancer cells. In this trial, participants will receive varying doses of TmPSMA-02 to assess its effectiveness and safety. TmPSMA-02 aims to improve outcomes and reduce immune-related side effects, which are common with these treatments. Although data on TmPSMA-02 in humans remains limited, the method is promising due to its specific targeting of cancer cells and expected lower toxicity. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TmPSMA-02

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.

How Is the Trial Designed?

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+

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/810537

autologous anti-PSMA CAR/CD2/dnTGF-BRII/PD-1:CD28 ... PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05489991

NCT05489991 | A Study of TmPSMA-02 Chimeric Antigen ... A Study of TmPSMA-02 Chimeric Antigen Receptor (CAR) T-cells in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC). ClinicalTrials.gov ID ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/C190115

Clinical Trials Using Autologous Anti-PSMA CAR/CD2 ... Review the clinical trials studying autologous anti-psma car/cd2/dntgf-brii/pd-1:cd28 switch receptor-expressing t-cells tmpsma-02 on this list and use the ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT357177

A CD2 endodomain containing double armored PSMA ... TmPSMA-02: A CD2 endodomain containing double armored PSMA CAR T with enhanced efficacy and lower immune toxicity. TmPSMA-02: A CD2 endodomain containing double ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10308799/

PSMA-targeting TGFβ-insensitive Armored CAR T-cells in ... Chimeric antigen receptor (CAR) T-cells have demonstrated promising efficacy, particularly in hematologic malignancies. A challenge for CAR T-cells in solid ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06046040

Study Details | NCT06046040 | TmPSMA-02 in mCRPC 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 ...