P-PSMA-101 CAR-T Cells for Prostate Cancer

Overseen By Clinical Trial Disclosure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Poseida Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active malignancy, Autoimmune, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called P-PSMA-101 CAR-T cells for certain prostate cancers. The goal is to assess the safety and effectiveness of this treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) or salivary gland cancer (SGC). Different groups receive varying doses to determine the best and safest application of the treatment. Ideal participants are those diagnosed with mCRPC or SGC who have experienced disease progression despite treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works 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 requires that you stop taking anti-cancer medications (except GnRH targeted therapies) and immunosuppressive medications at least 2 weeks before starting certain parts of the study. You should discuss your specific medications with the trial team to understand how they might be affected.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that P-PSMA-101 CAR-T cells hold promise in early studies. In these studies, P-PSMA-101 targeted prostate cancer cells in the lab and completely eliminated tumors in difficult-to-treat lab models. This success has prompted testing in humans.

P-PSMA-101 is a type of CAR-T cell therapy, using specially modified white blood cells to attack cancer. In trials, some similar therapies have been linked to side effects like fever and tiredness. However, specific safety data for P-PSMA-101 in people is still being gathered, as it is in its first phase of human testing. This phase focuses on understanding safety.

While the treatment is still new and more data is needed, early lab results are hopeful. For those considering joining a trial, this treatment shows potential, but discussing any concerns with the trial team is important. They can provide more detailed information about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for prostate cancer, which often involves hormone therapy, radiation, or chemotherapy, P-PSMA-101 CAR-T cells offer a unique approach by harnessing the body's immune system to target cancer cells directly. This treatment uses a novel mechanism of action: engineered T cells that specifically attack prostate cancer cells expressing the PSMA protein. Researchers are excited because CAR-T cell therapies have shown promise in other cancers, and this approach could provide a more precise and potentially more effective option for patients with prostate cancer. Additionally, the treatment includes both single and multiple dose strategies, allowing flexibility in administration and potential for personalized treatment plans.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that P-PSMA-101 CAR-T cells could effectively treat prostate cancer. In early tests with mice, these cells completely removed tumors, which is very encouraging. In human studies, after infusion into the blood, these cells grow and reach their peak levels about 2 to 3 weeks later. This growth correlates with a high number of special memory T cells that help fight cancer. The treatment targets a molecule called PSMA, found on prostate cancer cells, using a unique method to create the CAR-T cells. This trial will evaluate different dosing strategies of P-PSMA-101 CAR-T cells, including single and multiple dose regimens, to determine their effectiveness in finding and destroying prostate cancer cells. ^{1 2 3 4 5}

Who Is on the Research Team?

Rajesh Belani, M.D.

Principal Investigator

Sponsor Executive Medical Director

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced prostate cancer (mCRPC) or salivary gland cancers (SGC). Participants should be relatively healthy, able to perform daily activities with ease or minor difficulty (ECOG status of 0-1), and have organs functioning within certain limits. Men must agree to use birth control during the study and for two years after.

Inclusion Criteria

My cancer can be measured by scans or, if only in bones, by a PSA test showing at least 1 ng/mL.

I can carry out all my usual activities without help.

My vital organs are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Participants undergo leukapheresis to collect PBMCs, which are sent for manufacturing of P-PSMA-101 CAR-T cells

4-6 weeks

Treatment

Participants receive P-PSMA-101 CAR-T cells following a lymphodepleting chemotherapy regimen

4 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• P-PSMA-101 CAR-T cells
• Rimiducid

Trial Overview The trial is testing P-PSMA-101 CAR-T cells, a type of personalized immune cell therapy designed to target cancer cells in patients with mCRPC and SGC. It's an open-label study where everyone gets the treatment, and doses will increase gradually to find out how much can be given safely.

How Is the Trial Designed?

Group I: P-PSMA-101 CAR-T cells (Single Dose - Part 1c) Experimental Treatment 2 Interventions

Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.

Group II: P-PSMA-101 CAR-T cells (Single Dose - Part 1a) Experimental Treatment 2 Interventions

Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.

Group III: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d) Experimental Treatment 2 Interventions

Cyclic administration of ascending dose cohorts, given via intravenous infusions of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.

Group IV: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b) Experimental Treatment 2 Interventions

Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.

Who Is Running the Clinical Trial?

Poseida Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

780+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.098

Phase 1 study of P-PSMA-101 CAR-T cells in patients with ... P-PSMA-101 cells were shown to expand in blood via qPCR assay, peaking 2-3 weeks after infusion, consistent with the high percentage of TSCM.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04249947

Study Details | NCT04249947 | P-PSMA-101 CAR-T Cells ... This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-PSMA-101 to ...

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

PSCA-CAR T cell therapy in metastatic castration-resistant ... In the PSMA-targeting TGFβ-insensitive armored CAR T cell trial, the dose of CAR T cells was reduced after high-grade toxicity occurred (sepsis ...

4. urotoday.com urotoday.com/conference-highlights/asco-gu-2022/asco-gu-2022-prostate-cancer/135359-asco-gu-2022-phase-1-study-of-p-psma-101-car-t-cells-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc.html

ASCO GU 2022: Phase 1 Study of P-PSMA-101 CAR-T ... In preclinical mouse models of prostate cancer, P-PSMA-101 completely eliminated tumors. In this phase 1 trial (NCT04249947), the authors enrolled patients with ...

5. poseida.com poseida.com/wp-content/uploads/2023/04/P-PSMA-101-ASCO-GU2022-Speaker-Slides-27Jan22-FINAL.pdf

Phase 1 Study of P-PSMA-101 CAR-T Cells in Patients ... P-PSMA-101 is an autologous CAR-T therapy targeting PSMA and is made using a unique non-viral transposon system. (piggyBac®) that results in a CAR-T product ...