CAR T-Cell Therapy for Prostate Cancer

Overseen By Naomi Haas, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Active infection, Autoimmune disease, Cardiovascular disability, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day (Day 0)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-Cell therapy for prostate cancer that has spread and no longer responds to standard hormone treatments. The researchers aim to determine if this therapy is safe and can be administered without major issues. Participants will receive modified cells (CART-PSMA-TGFβRDN cells) that target cancer cells and resist certain growth signals. Those with prostate cancer that has spread, is resistant to usual treatments, and shows evidence of progression may be a good fit. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had treatment with certain immune therapies within 2 months before joining. You also cannot be on high-dose steroids, but low doses are allowed.

Is there any evidence suggesting that CART-PSMA-TGFβRDN cells are likely to be safe for humans?

Research has shown that CART-PSMA-TGFβRDN cells, a type of CAR T-cell therapy, have generally been well-tolerated in earlier studies. These studies examined the treatment's effectiveness for patients with prostate cancer unresponsive to standard treatments. Although some serious side effects occurred, the CAR T-cells were mostly safe for patients.

As this is early-stage research, the primary goal is to determine if the treatment can be safely administered. Some unknown side effects may still exist. However, previous studies provide reassurance that the treatment is tolerable at the tested doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CART-PSMA-TGFβRDN cells for prostate cancer because they take a unique approach compared to traditional treatments like hormone therapy, surgery, or radiation. This therapy uses CAR T-cells that are engineered to target PSMA, a protein often found in high levels on prostate cancer cells. Additionally, it includes a modification to reduce the effects of TGFβ, a molecule that typically hampers immune response, enhancing the treatment's effectiveness. This innovative strategy aims to harness the body's immune system to directly target and destroy cancer cells, potentially offering a more precise and powerful option for patients.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that a new treatment using CART-PSMA-TGFβRDN cells could be effective for prostate cancer. In this trial, participants will join different cohorts to receive varying doses of CART-PSMA-TGFβRDN cells. Earlier studies reported an average drop of 22.35% in patients' PSA levels, a key indicator for monitoring prostate cancer. Remarkably, one patient experienced a significant decrease in PSA levels within just two weeks. These specially designed cells aim to attack prostate cancer cells while avoiding the usual signals that inhibit the immune system. This makes them a promising option for treating difficult-to-manage prostate cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Naomi Haas, MD

Principal Investigator

Universtiy of Pennsylvania

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, showing at least 10% of tumor cells expressing PSMA. They should be relatively healthy (ECOG status 0-1), have good organ function, no severe heart issues or active infections like hepatitis B/C or HIV, not on high-dose steroids, and haven't had more than four prior treatments for this cancer stage.

Inclusion Criteria

My tumor shows high PSMA levels on a biopsy.

My cancer has spread to my bones or other parts of my body and can be seen on scans.

I have had treatment for advanced prostate cancer that no longer responds to hormonal therapy.

Exclusion Criteria

I have severe heart problems as defined by the NYHA.

I do not have a condition that increases risk of severe immune or nerve side effects.

I haven't had immune therapy for cancer in the last 2 months, except for cancer vaccines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of lentivirally transduced CART-PSMA-TGFβRDN cells, with or without lymphodepleting chemotherapy, depending on cohort assignment

1 day (Day 0)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and clinical anti-tumor effects

6 months

Long-term follow-up

Participants are monitored for long-term safety and adverse events

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART-PSMA-TGFβRDN cells

Trial Overview The trial is testing a new type of cell therapy where the patient's own immune cells are modified to target prostate cancer cells better. These special CART-PSMA-TGFβRDN cells are given through an IV after preparing the body with drugs Fludarabine and Cyclophosphamide.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells 0.70-1.00 x 10\^8 Day 0

Group II: Cohort 3 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells at the MTD (established by Cohorts 1-2) on day 0

Group III: Cohort 2 Experimental Treatment 1 Intervention

CART-PSMA-TGFβRDN cells 1-3x10\^8 Day 0

Group IV: Cohort 1 Experimental Treatment 1 Intervention

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Group V: Cohort -3 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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]

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]

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]

Citations

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

PSMA-targeting TGFβ-insensitive Armored CAR T-cells in ... The median observed PSA decline was 22.35% (range: 12% to 98.33%), including Patient 9 who rapidly achieved a PSA level of <0.1 ng/ml within 2 weeks of CART- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04227275

NCT04227275 | A Study of CART-PSMA-TGFβRDN in ... This is a Phase 1 single-arm study designed to identify the dose and regimen of CART-PSMA- TGFβRDN cells that can be safely administered intravenously following ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT324837

A phase I clinical trial of PSMA-directed/TGFβ-insensitive ... We conducted a first-in-human phase 1 clinical trial to evaluate the feasibility, safety and preliminary efficacy of PSMA-directed/TGFβ-insensitive CAR-T cells.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.094

Safety and early efficacy results from a phase 1, multicenter ... Safety and early efficacy results from a phase 1, multicenter trial of PSMA-targeted armored CAR T cells in patients with advanced mCRPC.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844023063557

Review article Chimeric antigen receptor-modified T cells ... They found that CAR-Ts targeting PSMA survived, proliferated, and recognized PSMA-positive cells in immunodeficient mice, demonstrating their ability to resist ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03089203

NCT03089203 | CART-PSMA-TGFβRDN Cells for Castrate ... This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04227275/

Clinical Trial: NCT04227275 This is a Phase 1 single-arm study designed to identify the dose and regimen of CART-PSMA- TGFβRDN cells that can be safely administered intravenously ...