CART-PSMA Cells for Advanced Prostate Cancer

Phase 1

Recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: CART-PSMA cells

• Registration Number: NCT05656573
• Lead Sponsor: Nova Therapeutics LLC

Brief Summary

This is a single center, open-label phase 1 study to assess the safety and feasibility of PSMA-specific CAR modified autologous T cells (CART-PSMA cells) in patients with advanced prostate cancer.

Detailed Description

Part A (Dose Escalation) + Part B (Expansion Cohort) total up to 20 patients enrolled.

Study Timeline

• Study First Submitted: 2022-12-01
• Study First Submitted QC: 2022-12-12
• Study First Posted: 2022-12-19
• Study Start: 2023-03-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

1. All participants must have the ability to understand and the willingness to sign a written informed consent.
2. Histologic confirmation of prostate cancer.
3. Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
5. Under general air conditions, blood oxygen saturation >90%.
6. Adequate liver function, specifically alanine aminotransferase (ALT) < 3 times of upper limit of normal (ULN), aspartate transferase (AST)< 3 times of ULN, serum bilirubin and alkaline phosphatase < 2 times of ULN.
7. Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
8. Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
9. Hemoglobin concentration ≥80g/L.
10. The side effects brought by the latest treatment should be recovered, and the latest chemotherapy should be at least 7 days before; At least three t½ have passed since the latest immunotherapy.

Exclusion Criteria

1. Patients with other malignant tumors or major diseases.
2. Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
3. Patients with uncontrolled active infection.
4. Patients with active hepatitis B or hepatitis C infection.
5. Patients with human immunodeficiency virus (HIV) infection.
6. Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
7. Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
8. Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
9. Patients with active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy.
10. Patients with active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS (cytokine release syndrome) or CAR Neurotoxicity.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
autologous CART-PSMA cells	CART-PSMA cells	Cohort 1： CART-PSMA cells 1-3x10\^7/M\^2(body surface area) on Day 0; Cohort 2： CART-PSMA cells 1-3x10\^8/M\^2(body surface area) on Day 0; Cohort 3： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10\^7/M\^2(body surface area) on Day 0. Cohort 4： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10\^8/M\^2(body surface area) on Day 0.

Primary Outcome Measures

Name	Time	Method
Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.	Up to 15 years	Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.

Secondary Outcome Measures

Name	Time	Method
The persistence, accumulation, and migration of CART-PSMA cells.	Up to 2 years	Assessing the trafficking of CART-PSMA cells in the peripheral blood by quantifying the mRNA of CAR gene at the time of each infusion as well as at each time of follow-up blood collection. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Overall survival (OS)	Up to 15 years	Estimating median OS from CART-PSMA cell infusion to the event date (death) or last contact date (censor date) by Kaplan Meier methods.
Serum cytokine profile	Up to 2 years	Assessing potential cytokine release syndrome (CRS) toxicity and CART cell effector function, sequential serum samples by analysis of Th1/Th2 cytokines (e.g., IL-2, IFNgamma, TNFalpha, IL-10, GMCSF, IL-6, MIP-1alpha) before and after CART-PSMA cell infusion.
Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy	Up to 2 years	Assessing phenotypes and frequencies of immune cell subsets in the peripheral blood, T cell subsets and phenotypes utilising groups of labelled antibodies.
Progression-free survival (PFS)	Up to 15 years	Estimating median PFS by survival without biochemical (PSA) or radiographic evidence of disease progression or relapse from CART-PSMA cell infusion to event date (progression/relapse or death); the censor date: off protocol therapy date (required disallowed treatment or withdrawal of consent for further therapy) or last contact date.
Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood	Up to 2 years	Assessing changes in levels of cfDNA to investigate if decreases in cfDNA levels correlate with response.
Patterns of change in PSA (prostate-specific antigen)	Up to 5 years	Assessing PSA response by the percentage of change in PSA from baseline to the defined time-frame on therapy (or earlier if patients discontinue therapy prior to the time-frame) as well as the maximum decline in PSA that occurs at any point during CART-PSMA cell infusion.
Changes in circulating tumor cells in peripheral blood	Up to 2 years	Assessing changes in levels of circulating tumor cells (CTC) to investigate if decreases in CTC levels correlate with response.

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, China