A Study of TmPSMA-02 Chimeric Antigen Receptor (CAR) T-cells in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

NCT05489991 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: TmPSMA-0201
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, multi-center, Phase 1/2 study to determine the safety, tolerability, and feasibility of dosing adult patients with mCRPC with genetically modified autologous T-cells (TmPSMA-02) engineered to express a CAR capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T-cell.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Chimeric Antigen Receptor (CAR); T-Cells; Prostate-Specific Membrane Antigen (PSMA); Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Phase 1: To evaluate the safety of TmPSMA-02 in adult patients with mCRPC

  Type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs)

  Up to 5 years

• Phase 1: To identify the recommended Phase 2 dose of TmPSMA-02 administered in combination with LD chemotherapy

  Frequency of DLTs and/or determination of the maximum tolerated dose (MTD)

  Up to 5 years

• Phase 2: To evaluate the objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

  Objective Response Rate (ORR) by RECIST v1.1.

  Up to 5 years

Secondary Outcomes (6)

• Phase 1: To evaluate the preliminary antitumor activity of TmPSMA-02 according to RECIST v1.1 and the PCWG3 criteria

  Up to 5 years

• Phase 1: To assess the clinical and manufacturing feasibility of TmPSMA-02

  Up to 5 years

• Phase 2: To evaluate the safety and tolerability of TmPSMA-02 in adult patients with mCRPC

  Up to 5 years

• Phase 2: Evaluate the anti-tumor activity of TmPSMA-02 according to Prostate Cancer Working Group 3 (PCWG3).

  Up to 5 years

• Phase 2: Describe pharmacokinetic factors of TmPSMA-02 in peripheral blood

  Up to 5 years

Study Arms (1)

TmPSMA-02

EXPERIMENTAL

Biological: TmPSMA-02

Interventions

TmPSMA-02 BIOLOGICAL

Intravenous administration of genetically modified autologous T-cells engineered to express a protein capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) with a lentiviral vector to express anti-PSMA scFv, CD2 co-stimulatory domain and dually armored with a dominant negative TGFβ receptor and PD1.CD28 switch, will be infused intravenously on Day 0 as a single flat dose following standard lymphodepleting (LD) regimen.

TmPSMA-02

Eligibility Criteria

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

You may qualify if:

• Adults at least 18 years of age.
• A confirmed histologic diagnosis of prostate cancer.
• Castrate levels of testosterone (\< 50 ng/dL).
• Measurable disease (radiographic or Prostate Specific Antigen \[PSA\]) per PCWG3 criteria (see Appendix 3)
• Received at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor (e.g., enzalutamide or apalutamide) or CYP17α inhibitor (e.g., abiraterone/ prednisone) and a taxane based regimen (e.g., docetaxel, cabazitaxel, etc). At least one line of prior therapy must be in the mCRPC setting. Note: Androgen deprivation therapy (ADT) with gonadotropin- releasing hormone (GnRH) agonist/antagonist does not count as a line of therapy nor does a first-generation nonsteroidal antiandrogen (e.g., bicalutamide, flutamide, etc.).
• Adequate vital organ function as defined by: (A) Estimated glomerular filtration rate (eGFR) eGFR ≥ 50 mL/min by Modification of Diet in Renal Disease criteria, (B) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 ULN. (C) Serum total bilirubin \< 1.5 × ULN unless patient has known Gilbert's; if so, then serum bilirubin ≤ 3 mg/dL, or (D) Left ventricular ejection fraction ≥ 45%.
• Patients must have adequate hematologic reserve and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as: (A) Hemoglobin ≥ 8 g/dL, (B) absolute neutrophil count ≥ 1000/ μL, or (C) Platelet count ≥ 75,000/μL.
• Patients who have not undergone bilateral orchiectomy must be able to continue GnRH therapy during the study.
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Toxicities from any previous therapy must have recovered to Grade 1 or to the baseline. Exceptions include non-clinically significant toxicities as a result of previous therapy (e.g., alopecia, hormonal changes, weight loss, etc).
• Patients of reproductive potential agree to use protocol-specified highly effective contraceptive methods

You may not qualify if:

• Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer may still be eligible\], unless treated with curative intent, i.e., non-melanoma skin cancer.
• Prior treatment with autologous T-cell therapy. Note: Prior treatment with Sipuleucel-T is allowed.
• Patients who require chronic treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day). Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable.
• Prior allogeneic stem cell transplant.
• Active autoimmune disease (including, but not limited to, connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy. Patients should have stopped any immunosuppressive therapy within 6 weeks prior to Screening.
• Current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Viral testing at Screening is required in all patients to rule out subclinical infections. Patients who are hepatitis B core antibody positive and hepatitis B surface antigen negative should have quantitative viral load measured. If viral load is undetectable, the patient may enroll and be monitored as per ASCO Guidelines.
• Seizure disorder requiring anti-epileptic medications.
• History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients (e.g., human serum albumin, dimethyl sulfoxide \[DMSO\], dextran 40) that would preclude the patient safely receiving TmPSMA-02.
• History of or known predisposition to hemophagocytosis lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
• Active or recent (within the past 6 months prior to leukapheresis) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina or (3) a history of recent (within 6 months) myocardial infarction or sustained (\> 30 second) ventricular tachyarrhythmias, (4) cerebrovascular accident.
• Active or uncontrolled medical or psychiatric condition that would preclude participation in the opinion of the Sponsor, Principal Investigator (PI) and/or their designee.
• Have inadequate venous access for or contraindications for the leukapheresis procedure. Central venous access is acceptable.

Sponsors & Collaborators

• Tceleron Therapeutics, Inc.: lead

Study Sites (1)

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

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

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: August 5, 2022
• Study Start: September 6, 2022
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

US (1)