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.
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
Drug | Synonyms | Arms |
---|
CART-PSMA-TGFβRDN | | Dose Escalation |
Cyclophosphamide | | Dose Escalation |
Fludarabine | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation | Experimental | Dose 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