Clinical Trials /

A Study of CART-PSMA-TGFβRDN in Patients With Metastatic Castration Resistant Prostate Cancer

NCT04227275

Description:

Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate cancer (mCRPC) with genetically modified autologous T cells (CART-PSMA-TGFβRDN cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T cell.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CART-PSMA-TGFβRDN in Patients With Metastatic Castration Resistant Prostate Cancer
  • Official Title: A Phase 1 Open-Label, Multi-Center Study of PSMA Targeted Genetically Modified Chimeric Antigen Receptor T Cells in Patients With Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: CART-PSMA-TGFβRDN-02
  • NCT ID: NCT04227275

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
CART-PSMA-TGFβRDNDose Escalation
CyclophosphamideDose Escalation
FludarabineDose Escalation

Purpose

Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate cancer (mCRPC) with genetically modified autologous T cells (CART-PSMA-TGFβRDN cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T cell.

Detailed Description

      This is a Phase 1 single-arm study designed to identify the dose and regimen of CART-PSMA-
      TGFβRDN cells that can be safely administered intravenously following the lymphodepletion
      (LD) regimen to patients with metastatic castration resistant prostate cancer (mCRPC).

      It is anticipated that approximately 18 patients will enroll in this study.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose escalation of intravenous CART-PSMA-TGFβRDN cells for patients with metastatic castration resistant prostate cancer
  • CART-PSMA-TGFβRDN
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed histologic diagnosis of prostate cancer and have mCRPC

          -  Prior therapies defined as at least 2 prior lines of systemic therapy for prostate
             cancer, including at least one second generation androgen receptor inhibitor and/or
             CYP17α inhibitor. At least one line of prior therapy must be in the mCRPC setting

          -  Evidence of disease as defined as castrate levels of testosterone (<50 ng/mL) AND
             Evidence of one of the following measures of progressive disease in the 12 weeks
             preceding eligibility confirmation by physician: i.) Soft tissue progression by
             Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; ii.) Osseous
             disease progression with 2 or more new lesions on bone scan; iii.) Increase in serum
             PSA of at least 25% and an absolute increase of 2 ng/mL or more from nadir on at least
             three consecutive tests a minimum of 1 week apart

          -  PSMA+ disease determined by centrally tested PSMA expression in prior or archival
             tumor sample

          -  Evaluable disease per Prostate Working Group 3 (PCWG3) criteria

          -  Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

          -  Life expectancy of greater than 3 months

          -  Toxicities from any previous therapy must have recovered to Grade 1 or baseline

          -  Patients who have not undergone bilateral orchiectomy must be able to continue
             gonadotropin-releasing hormone (GnRH) therapy during the study

          -  Estimated creatinine clearance ≥ 60 mL/min by Modification of Diet in Renal Disease
             criteria

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x the upper
             limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 x ULN

          -  Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then
             serum bilirubin ≤3 mg/dL

          -  Serum albumin ≥ 3.0 g/dL

          -  Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been
             performed within 8 weeks of enrollment

          -  Hemoglobin ≥ 9 g/dL

          -  Absolute neutrophil count ≥ 1500/μL

          -  Platelet count ≥ 100,000/μL

          -  Patients of reproductive potential agree to use of approved highly effective
             contraceptive methods

        Exclusion Criteria:

          -  Active invasive cancer, other than the proposed cancer included in the study, within 2
             years prior to screening, unless treated with curative intent

          -  Current treatment with systemic corticosteroids (defined as a dose greater than the
             equivalent of prednisone 10 mg/day)

          -  Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis,
             inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune
             disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy
             within 6 weeks prior to screening visit)

          -  Current, active human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B
             virus infections

          -  Prior allogeneic stem cell transplant

          -  Active and untreated central nervous system malignancy

          -  History of severe infusion reaction to monoclonal antibodies or biological therapies,
             or to study product excipients that would preclude the patient safely receiving
             CART-PSMA-TGFβRDN cells

          -  History of being previously treated with a J591 antibody-based therapy

          -  Active or recent (within the past 6 months prior to apheresis) cardiac 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

          -  Have inadequate venous access for or contraindications for the apheresis procedure

          -  Must agree not to participate in a conception process or must agree to a highly
             effective method of contraception
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Identification of CART-PSMA-TGFβRDN
Time Frame:Up to 2 years
Safety Issue:
Description:Incidence of Dose Limiting Toxicity (DLT)

Secondary Outcome Measures

Measure:Safety of CART-PSMA-TGFβRDN
Time Frame:Up to 2 years
Safety Issue:
Description:Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and severity grade
Measure:Tolerability of CART-PSMA-TGFβRDN
Time Frame:Up to 2 years
Safety Issue:
Description:Various measures of safety will be tabulated by dose level and intensity grade, including the incidence of treatment emergent AEs
Measure:Preliminary efficacy of CART-PSMA-TGFβRDN as assessed by biochemical Objective Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR defined as the proportion of patients with maximal prostate-specific antigen (PSA) decline of greater than or equal to 50% at 12 weeks post infusion
Measure:Feasibility of CART-PSMA-TGFβRDN
Time Frame:Up to 2 years
Safety Issue:
Description:Proportion of patients who did not receive CART-PSMA-TGFβRDN cells
Measure:Peripheral expansion and persistence of CART-PSMA-TGFβRDN
Time Frame:Up to 15 years
Safety Issue:
Description:Quantitative polymerase chain reaction (qPCR)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tmunity Therapeutics

Trial Keywords

  • Chimeric Antigen Receptor (CAR)
  • T-cells
  • Prostate-Specific Membrane Antigen (PSMA)
  • Prostate Cancer

Last Updated

January 9, 2020