Engineered T Cell Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Radiopharmaceuticals, Corticosteroids, Immunosuppressives, others

Disqualifiers: Non-prostate cancer, Autoimmune diseases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for prostate cancer using the patient's own T cells, which have been modified to recognize and destroy cancer cells. The goal is to determine the safety of these engineered autologous T cells and understand their effects on the cancer and the patient’s body. The study seeks men with advanced prostate cancer that has spread despite hormone treatments. Participants should have progressive cancer affecting their bones or other tissues. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain treatments and medications, like some radiopharmaceuticals and alternative medicine treatments for prostate cancer, should not be taken within four weeks before starting the study. It's best to discuss your specific medications with the study team.

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

Research has shown that specially engineered T cells have been tested for safety in prostate cancer patients. In these studies, patients received their own T cells, modified to better target cancer cells. The aim was to determine if these modified T cells could help fight cancer without causing major side effects.

In one study, the treatment proved safe, and some patients experienced a noticeable drop in prostate-specific antigen (PSA) levels, suggesting the treatment might be effective. However, as this is a new approach for prostate cancer, researchers continue to study all possible side effects.

Another study on a similar T cell therapy found it was well-tolerated, with most patients not experiencing severe side effects. Researchers are still investigating how different doses affect safety and effectiveness.

Overall, while early results are promising, the safety of this treatment remains under close observation. Potential participants should understand that this is part of ongoing research to determine both the benefits and risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about engineered autologous T cells for prostate cancer because these cells are designed to target Prostate-Specific Membrane Antigen (PSMA) directly. Unlike traditional treatments such as surgery, radiation, or hormone therapy, which can affect healthy tissues as well, these engineered T cells offer a highly specific approach by honing in on cancer cells that express PSMA. Additionally, the use of cyclophosphamide as a pretreatment helps create a more favorable environment for these T cells to thrive and attack cancer cells effectively. This targeted approach could potentially lead to fewer side effects and more effective cancer cell eradication.

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

Research has shown that specially designed T cells, engineered to attack prostate cancer cells, have shown promise in early studies. In one study, patients experienced an average drop of 22.35% in PSA levels, a marker used to track prostate cancer. Another study highlighted the potential of CAR T cell therapy, similar to the engineered T cells tested in this trial, as a promising method for treating hard-to-treat cancers. While the best results often occur in blood cancers, these findings suggest potential for treating prostate cancer. This trial will assess the safety and tolerability of engineered autologous T cells, administered after pretreatment with cyclophosphamide, to help the immune system better recognize and destroy cancer cells. ^{1 3 6 7 8}

Who Is on the Research Team?

Susan F. Slovin, MD, Ph.D

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for men over 18 with advanced prostate cancer that has spread and is resistant to hormone therapy. They must have a good performance status, adequate organ function, no HIV or hepatitis, and agree to use contraception. Excluded are those with other cancers within five years (except non-melanoma skin cancer), severe heart or lung disease, recent radiation therapy, immunosuppressive treatments, certain medications for prostate cancer, active CNS metastases, infections requiring antibiotics shortly before the trial starts.

Inclusion Criteria

I am mostly able to care for myself but may not be able to do active work.

My cancer has spread to my bones, confirmed by scans.

Lab requirements met for Hematology and Serum Chemistry

Exclusion Criteria

Positive stool guaiac test, excluding specific conditions

Medical conditions interfering with study participation

I have not had any cancer other than non-melanoma skin cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pretreatment

Participants receive pretreatment with cyclophosphamide before T cell infusion

1 day

Treatment

Participants receive engineered autologous T cells targeted to PSMA

1 day

Follow-up

Participants are monitored for safety and effectiveness after T cell infusion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• cyclophosphamide
• engineered autologous T cells

Trial Overview The study tests different doses of modified T cells from the patient's own body designed to target and kill prostate cancer cells. It's a phase I safety trial aiming to see how these engineered immune cells affect both the body and the progression of prostate cancer.

How Is the Trial Designed?

Group I: autologous T cells & cyclophosphamide. Experimental Treatment 2 Interventions

This is a phase I dose escalation study to assess the safety and tolerability using increasing doses of engineered autologous T cells targeted to Prostate-Specific Membrane Antigen (PSMA) administered one day after pretreatment with cyclophosphamide.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Recent advancements in delivering transgenes to human T cells have improved the effectiveness of T cell therapies for cancer, allowing for the creation of T cells that can specifically target tumors.

While genetically modified T cells have shown success in clinical trials, they can also cause significant on-target toxicity, highlighting the need for careful selection of target antigens and strategies to manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered T cells for anti-cancer therapy. Turtle, CJ., Hudecek, M., Jensen, MC., et al.[2021]

The study identified STEAP2 as a promising target for CAR-T therapy in prostate cancer due to its high expression on tumor cells and limited presence in normal tissues, reducing the risk of off-target effects.

The engineered CAR-T therapy, AZD0754, showed strong anti-tumor activity in both laboratory and mouse models, demonstrating its potential as a safe and effective treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. Zanvit, P., van Dyk, D., Fazenbaker, C., et al.[2023]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

CAR-T cell therapies have shown significant clinical success in treating cancer by effectively targeting tumor-associated antigens, leading to complete and durable responses in many patients during early trials.

Despite their effectiveness, there are safety concerns regarding potential toxicities from engineered cells, prompting the exploration of strategies like integrating failsafe switches to enhance safety in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns. Resetca, D., Neschadim, A., Medin, JA.[2018]

T-cell receptor gene therapy shows promise in redirecting T lymphocytes to target tumors, leading to encouraging clinical responses in previously incurable cancers, but it faces significant challenges in ensuring safety and efficacy.

Identifying specific tumor epitopes that can effectively target cancer cells while avoiding damage to normal tissues is crucial, and there is a need for improved preclinical methods to assess potential risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell receptor gene therapy--ready to go viral? Karpanen, T., Olweus, J.[2021]

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

PSCA-CAR T cell therapy in metastatic castration-resistant ... This study validates PSCA as a viable CAR T cell therapeutic target and provides encouraging early clinical data to support further studies, ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.708073/full

PSMA-Specific CAR-Engineered T Cells for Prostate Cancer Remarkable clinical outcomes were evidenced in hematological malignancies after injection of CD19 CAR T cells, overall establishing the concept ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06193486

Study Details | NCT06193486 | Autologous Gamma Delta T ... This clinical trial includes a dose-escalation phase and dose-expansion phase to assess the safety and preliminary efficacy of treatment with autologous T cells ...

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

Review article Chimeric antigen receptor-modified T cells ... Chimeric antigen receptor-modified T cell (CAR-T) therapy, a type of immunotherapy, has shown significant efficacy in treating hematologic malignancies [14] ...

6. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27324746/

Phase I Trial of Anti-PSMA Designer CAR-T Cells in ... Under a Phase I dose escalation in prostate cancer, a 20% engraftment target was met or exceeded in three subjects with adequate safety, leading to study ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04227275

NCT04227275 | A Study of CART-PSMA-TGFβRDN in ... Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate ...