CART-PSMA-TGFβRDN Cells for Castrate-Resistant Prostate Cancer

• Status: Active, not recruiting
• Trial end date: 2021-09-08
• Target enrollment: 0
• Participant gender: Male

Summary

This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/ TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.

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

Details

• Lead Sponsor: University of Pennsylvania
• Treatments: Cyclophosphamide

Criteria

Inclusion Criteria:

• Metastatic castrate resistant prostate cancer

≥10% tumor cells expressing PSMA as demonstrated by immunohistochemistry analysis on fresh tissue.

• Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral)

• Patients > or = 18 years of age

• ECOG performance status of 0 - 1

• Adequate organ function, as defined by:

• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min

• Serum total bilirubin < 1.5x ULN

• Serum ALT/AST < 2x ULN

• Adequate hematologic reserve within 4 weeks of study enrollment as defined by:

• Hgb > 10 g/dl

• PLT > 100 k/ul

• ANC > 1.5 k/ul

• Note: Subjects must not be transfusion dependent

• Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by:

• Castrate levels of testosterone (< 50 ng/ml) with or without the use of androgen deprivation therapy AND

• Evidence of one of the following measures of progressive disease in the 12 weeks preceding study enrollment: soft tissue progression by RECIST 1.1 criteria, osseous disease progression with 2 or more new lesions on bone scan(as per PCWG2 criteria), increase in serum PSA of at least 25% and an absolute increase of 2ng/ml or more from nadir (as per PCWG2 criteria)

• Prior therapy with at least one standard 17α lyase inhibitor or second-generation anti-androgen therapy for the treatment of metastatic castrate resistant prostate cancer

• Provides written informed consent

• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria:

• Prior treatment with an immune-based therapy for the treatment of prostate cancer, including cancer vaccine therapies (such as SipuleucelT, PROSTVAC) are allowable. Under protocol-specified conditions, immune checkpoint inhibitors,radium-223 and immunoconjugate therapies are also allowable.

• History of an active non-curative non-prostate primary malignancy within the prior 5 years

• Subjects who require the chronic use of systemic corticosteroid therapy. Patients may be on a low dose of steroids (≤10mg equivalent of prednisone).

• Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification

• Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or MRI imaging)

• History of active or severe autoimmune disease requiring immunosuppressive therapy

• Patients with ongoing or active infection.

• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO,and Dextran 40)

• Active hepatitis B, hepatitis C or HIV infection.