TmPSMA-02 in mCRPC

NCT06046040 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: UPCC 11823
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.

Conditions

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

Outcome Measures

Primary Outcomes (3)

• Number of subjects with dose limiting toxicities (DLTs)

  28 days after TmPSMA-02 CAR T cell infusion

• Determination of maximum tolerated dose (MTD)

  28 days after TmPSMA-02 CAR T cell infusion

• Incidence of Adverse Events as assessed by CTCAE v5.0

  Up to 15 years

Secondary Outcomes (6)

• Percentage of manufacturing products that meet release criteria

  Up to 3 years

• Overall Response Rate (ORR)

  Up to 3 months

• Duration of Response (DOR)

  up to one year

• Progression Free Survival (PFS)

  Up to one year

• Overall Survival (OS)

  Up to one year

Study Arms (4)

Dose Level -1

EXPERIMENTAL

After lymphodepleting chemotherapy subjects to receive 1x10(7) TmPSMA-02 CAR T Cells

Drug: TmPSMA-02 CAR T Cells

Dose Level 1

EXPERIMENTAL

After lymphodepleting chemotherapy subjects to receive 5 x10(7) TmPSMA-02 CAR T Cells

Drug: TmPSMA-02 CAR T Cells

Dose Level 2

EXPERIMENTAL

After lymphodepleting chemotherapy subjects to receive 1x10(8) TmPSMA-02 CAR T Cells

Drug: TmPSMA-02 CAR T Cells

Dose Level 3

EXPERIMENTAL

After lymphodepleting chemotherapy subjects to receive 3x10(8) TmPSMA-02 CAR T Cells

Drug: TmPSMA-02 CAR T Cells

Interventions

TmPSMA-02 CAR T Cells DRUG

TmPSMA-02 CAR T cells: autologous T cells transduced with a lentiviral vector to express an anti-PSMA CAR containing a humanized J591-derived scFv and CD2 co-stimulatory domain, and dually armored with a TGFβRDN and PD1.CD28 switch receptor.

Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written informed consent
• Adult participants ≥ 18 years of age
• Metastatic castrate-resistant prostate cancer (mCRPC)
• Castrate levels of testosterone (\<50 ng/dL) with/without the use of androgen-deprivation therapy
• 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).
• Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:
• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis
• ALT/AST ≤ 3 x ULN
• 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)
• Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• 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:
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1000/μL
• Platelet count ≥ 75,000/μL

You may not qualify if:

• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
• Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
• 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.
• Prior treatment with autologous T-cell therapy, with the exception of Sipuleucel-T.
• Prior allogeneic stem cell transplant.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Sponsors & Collaborators

• University of Pennsylvania: lead
• Prostate Cancer Foundation: collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• Wang Y, Zhao G, Wang S, Li N. DNTGF-betaR armored CAR-T cell therapy against tumors from bench to bedside. J Transl Med. 2024 Jan 11;22(1):45. doi: 10.1186/s12967-023-04829-6. No abstract available.

  PMID: 38212769 DERIVED

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 21, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2042
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

US (1)