Using TmPSMA-02 CAR T cells for advanced prostate cancer

Phase I, Open-Label Study of Dually Armored Chimeric Antigen Receptor (CAR) T Cells (TmPSMA-02) in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

This study is testing a new type of CAR T cell therapy to see if it can safely help people with advanced prostate cancer that hasn't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: prednisone, CAR T, cyclophosphamide, fludarabine
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06046040 on ClinicalTrials.gov

What this trial studies

This Phase I, open-label dose finding study evaluates the safety, tolerability, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study employs a 3+3 dose escalation design to assess up to four total dose levels, starting with a single dose of TmPSMA-02 CAR T cells administered via IV infusion after lymphodepletion. The goal is to determine the maximum tolerated dose while monitoring for dose-limiting toxicities (DLTs) and overall patient response.

Who should consider this trial

Good fit: Ideal candidates are adult men aged 18 and older with metastatic castrate-resistant prostate cancer who have previously received standard systemic treatments.

Not a fit: Patients who have not been diagnosed with metastatic castrate-resistant prostate cancer or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with advanced prostate cancer that is resistant to standard therapies.

How similar studies have performed: Other studies using CAR T cell therapies have shown promise in treating various cancers, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Signed, written informed consent
2. Adult participants ≥ 18 years of age
3. Metastatic castrate-resistant prostate cancer (mCRPC)
4. Castrate levels of testosterone (\<50 ng/dL) with/without the use of androgen-deprivation therapy
5. Received at least one prior standard therapy for systemic treatment in the mCRPC setting, including at least one second generation androgen receptor signaling inhibitor (e.g., enzalutamine, apalutamide, darolutamide, or abiraterone) or a taxane-based regimen (e.g., docetaxel, cabazitaxel, etc).
6. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:

   1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis
   2. ALT/AST ≤ 3 x ULN
   3. Serum total bilirubin ≤ 1.5 mg/dL, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤3.0 mg/dL)
   4. Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO
   5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
7. Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:

   1. Hemoglobin ≥ 8 g/dL
   2. Absolute neutrophil count ≥ 1000/μL
   3. Platelet count ≥ 75,000/μL
8. ECOG Performance Status that is either 0 or 1.
9. Patients who have not undergone bilateral orchiectomy must be able to continue GnRH therapy during the study.
10. Participants of reproductive potential must agree to use acceptable birth control methods, as described in the protocol.

Exclusion Criteria:

1. Active hepatitis B or hepatitis C infection
2. Any other active, uncontrolled infection
3. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
4. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
5. Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
6. Patients requiring chronic treatment systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.6.
7. Prior treatment with autologous T-cell therapy, with the exception of Sipuleucel-T.
8. Prior allogeneic stem cell transplant.
9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Where this trial is running

Philadelphia, Pennsylvania

• Abramson Cancer Center of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: Abramson Cancer Center Clinical Trials Service

Conditions Metastatic Castrate-Resistant Prostate Cancer