CAR T-cell Therapy for Prostate Cancer

Overseen By Ngan Vu

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Center

Must be taking: Platinum-based chemotherapy

Must not be taking: Steroids, Anti-arrhythmia therapy

Disqualifiers: HIV, Hepatitis B, Heart failure, others

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

Compensation: Varies

Number of Visits: 5

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

Research Team

Michael Schweizer

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with small cell neuroendocrine prostate cancer that's advanced locally or spread elsewhere and can't be surgically removed. They must have had platinum-based chemo, no severe chronic respiratory illness, brain metastases, significant heart issues, uncontrolled infections or certain autoimmune diseases in the last 5 years. Participants need to agree to contraception use and have a life expectancy over 3 months.

Inclusion Criteria

Your body has enough infection-fighting white blood cells.

My tumor is L1CAM positive based on a special lab test.

My cancer can be measured by scans.

Exclusion Criteria

Your blood sodium level is less than 130 mEq/L before starting the study.

You have other medical or mental health conditions that could make it hard to understand the study results or complete the study.

I have a serious lung condition like COPD diagnosed in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and Bridging Therapy

Patients undergo leukapheresis to obtain PBMCs for T cell product manufacturing and may undergo bridging therapy

1-2 weeks

1 visit (in-person)

Lymphodepleting Chemotherapy and CAR T Cell Infusion

Patients undergo lymphodepleting chemotherapy followed by an autologous L1CAM-specific CAR+EGFRt+ T cell infusion

1 week

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly for 3 months, then every 3 months

Long-term Follow-up

Participants may undergo long-term follow-up annually

Up to 15 years

Treatment Details

Interventions

• Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors

Trial Overview The trial tests autologous CAR T-cell therapy using patients' own immune cells modified to target L1CAM protein on tumor cells. It aims to determine the best dose and side effects of these engineered T-cells in treating advanced prostate cancer that expresses L1CAM.

Participant Groups

Group I: Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells) Experimental Treatment 13 Interventions

Patients undergo leukapheresis to obtain PBMCs for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide IV and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or PI. Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cells infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients also undergo ECHO or MUGA during screening. Patients undergo x-ray imaging, CT, bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania