Image

TmPSMA-02 in mCRPC

Recruiting
18 years of age
Male
Phase 1

Powered by AI

Overview

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.

Description

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 as described below. Dose escalation will begin with Dose Level 1 as follows:

  • Dose Level 1 (N = 3 to 6): Subjects will receive a single dose of 5 x 107 TmPSMA-02 CAR T cells via IV infusion administration on Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows:
  • If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level.
  • If 0 DLT/3 subjects or 1 DLT/6 subjects occur, the study will advance to Dose Level 2 (DL2).
  • In the event that 2 or more DLTs occur at Dose Level 1 (DL1), enrollment at this dose level will be stopped and Dose Level -1 (DL-1) will be opened. In Dose Level -1, subjects will receive a de-escalated dose of 1 x 107 TmPSMA-02 CAR T cells following lymphodepletion.

If 0 DLT/3 or 1 DLT/3 subjects occurs at DL-1, the study will enroll an additional 3 subjects at this dose level.

If ≥ 2 DLTs occur at any time, enrollment at this dose level will be stopped.

Dose Level 2 (N = 3 to 6): Subjects will receive a single fixed dose of 1 x 108 TmPSMA-02 CAR T cells via IV infusion on Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows:

  • If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level.
  • If 0 DLT/3 subjects or 1 DLT/6 subjects occur, the study will advance to Dose Level 3 (DL3).
  • If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If less than 6 subjects were treated at the previous dose level (DL1), additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination.

• Dose Level 3 (N = 3 to 6): Subjects will receive a single fixed dose of 3 x 108 TmPSMA-02 CAR T cells via IV infusion Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows:

  • If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level.
  • If 0 DLT/3 subjects occurs, the study will still enroll an additional 3 subjects at this dose level to allow for MTD determination.
  • If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If less than 6 subjects were treated at the previous dose level (DL2), additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination.

The highest dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects will be declared the MTD.

Retreatment Infusions:

The Retreatment Phase will remain closed until sufficient safety and persistence data is available in initial subjects, and DSMB and FDA approval to open Retreatment has been received.

Subjects who have demonstrated clinical benefit after their initial TmPSMA-02 CAR T cell infusion (e.g., minimum disease response of stable disease, etc.) may also be eligible to receive retreatment with TmPSMA-02 CAR T cells at the physician-investigator's discretion. The TmPSMA-02 retreatment dose administered must either be a) the CAR T cell dose that the subject previously received without DLTs, or b) a CAR T cell dose that is less than or equal to a dose level that has been evaluated for safety in ≥ 3 other subjects without evidence of DLTs. As retreatment infusions will not be used for formal DLT assessments/MTD determination, there are no protocol-defined staggering requirements.

Eligibility

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).

Study details

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

NCT06046040

University of Pennsylvania

15 February 2024

Step 1 Get in touch with the nearest study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

FAQs

Learn more about clinical trials

What is a clinical trial?

A clinical trial is a study designed to test specific interventions or treatments' effectiveness and safety, paving the way for new, innovative healthcare solutions.

Why should I take part in a clinical trial?

Participating in a clinical trial provides early access to potentially effective treatments and directly contributes to the healthcare advancements that benefit us all.

How long does a clinical trial take place?

The duration of clinical trials varies. Some trials last weeks, some years, depending on the phase and intention of the trial.

Do I get compensated for taking part in clinical trials?

Compensation varies per trial. Some offer payment or reimbursement for time and travel, while others may not.

How safe are clinical trials?

Clinical trials follow strict ethical guidelines and protocols to safeguard participants' health. They are closely monitored and safety reviewed regularly.
Add a private note
  • abc Select a piece of text.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.