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

• Status: Active, not recruiting
• Trial end date: 2036-11-30
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tmunity Therapeutics
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

• Confirmed histologic diagnosis of prostate cancer and have mCRPC, with castrate levels of testosterone (<50 ng/mL)

• PSA measurable disease per Prostate Working Group 3 (PCWG3) criteria

• 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

• Estimated estimated glomerular filtration rate ≥ 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 ≥ 8 g/dL

• Absolute neutrophil count ≥ 1000/μL

• Platelet count ≥ 75,000/μL

• Patients who have not undergone bilateral orchiectomy must be able to continue gonadotropin-releasing hormone (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 baseline

• 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 human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus infections; Patients who are hepatitis B core antigen positive, hepatitis B surface antigen negative, should have a quantitative viral load measured; If viral load is undetectable, the patient will not be excluded if hey are able to be treated with anti-viral medication for at least 7 days prior to lymphodepletion until at least 6 months after infusion with viral load and ALT monitoring

• Active or uncontrolled medical or psychological condition that would preclude participation

• History of seizure disorder

• Prior allogeneic stem cell transplant

• 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

• Ferritin levels ≥ 4x the upper limit of normal prior to apheresis or prior to the start of lymphodepleting chemotherapy

• Active or recent (within the past 6 months prior to apheresis or lymphodepletion) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina, (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident

• Any active infection currently being treated or any infection within the last 6 weeks that required 7 days or more of IV antibiotics or any active infection within the last 4 weeks that requires use of oral antibiotics. Patients may be eligible once these timeframes elapse and with evidence that the infection has completely resolved

• 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