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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment where a patient's immune cells are modified to better fight advanced prostate and salivary gland cancers. The modified cells are reintroduced into the body to target and destroy cancer cells.

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 P-PSMA-101 CAR-T cell therapy safe for humans?

Early studies on PSMA-targeting CAR T cells, including those with a dominant-negative TGFβ receptor, show that they are generally safe and feasible for treating prostate cancer. However, challenges such as dose-limiting toxicity and immune-related side effects have been noted in clinical trials. ^{1 2 3 4 5}

How is the P-PSMA-101 CAR-T cell treatment different from other prostate cancer treatments?

P-PSMA-101 CAR-T cells are unique because they are engineered to specifically target the prostate-specific membrane antigen (PSMA) on prostate cancer cells, potentially offering a more precise attack on the cancer compared to traditional treatments. This approach uses the patient's own immune cells, which are modified to better recognize and destroy cancer cells, and represents a novel strategy in treating prostate cancer, especially in cases where other treatments have failed. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment P-PSMA-101 CAR-T cells for prostate cancer?

Research shows that CAR-T cell therapy, which involves modifying a patient's immune cells to target cancer cells, has shown promise in treating prostate cancer by specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells. Early clinical studies have demonstrated antitumor activity, suggesting potential effectiveness in prostate cancer treatment. ^{1 2 3 6 8}

Research Team

Rajesh Belani, M.D.

Principal Investigator

Sponsor Executive Medical Director

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

[Current Trend of CAR-T Cell Therapy for Metastatic Castration-Resistant Prostate Cancer]. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen. [2020]

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

Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. [2021]

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

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