LIGHT-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer

A Phase I Study to Evaluate the Safety and Efficacy of PSMA-CART Co-expressing LIGHT in Treating Patients With Castrate-Resistant Prostate Cancer (CRPC)

This is a single center, single arm Phase I study to establish the safety and efficacy of intravenously administered lentivirally transduced LIGHT-PSMA-specific CAR modified autologous T cells (PSMA-CART cells) in patients with CRPC.

Study Overview

• Status: Suspended
• Conditions: Castrate-Resistant Prostate Cancer
• Intervention / Treatment: Biological: LIGHT-PSMA-CART cells

Detailed Description

This is a Phase I study evaluating the safety and efficacy of PSMA targeting autologous CAR T cells co-expressing LIGHT in a 3+3 dose escalation design. Cohort 1 subjects (N=3 or 6) will receive a tolal dose of 3x 10^6/kg body weight (KgBW) LIGHT-PSMA-CART cells at split doses after a conditioning chemotherapeutic regimen(Cy+Flu). If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs, the study will advance to Cohort 2, with a total dose of 6 x 10^6/ KgBW.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fully understand and voluntarily sign informed consent.
• Male, aged 18 to 75 years old.
• Expected survival > 6 months.
• CRPC patients: Prostate cancer is still progressing after continuous androgen deprivation therapy. Including, castrate levels of serum testosterone (<50ng/dl or <1.7nmol/L); or prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, and PSA>1 ug/L; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response.
• CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastasis).
• Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%.
• ECOG score <2.
• Hgb > 10 g/dl.
• PLT > 100×109/L.
• ANC > 1.5×109/L.

Exclusion Criteria: Subjects who meet any of the following exclusion criteria will be excluded

• Prior treatment with any immunotherapy, including CART therapy, tumor vaccine therapy, radium-223, checkpoint inhibitors.
• Prior treatment with any PSMA targeting therapy.
• Subjects with severe mental disorders.
• Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (LVEF < 55%) was decreased by echocardiography or MUGA scan (within 8 weeks before PBMC collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis.
• Patients with ongoing or active infection.
• Aspartate aminotransferase or Alanine aminotransferase >2.5*ULN; CK>1.5*ULN; CK-MB>1.5*ULN; TnT>1.5*ULN.
• Total bilirubin >1.5*ULN.
• Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment.
• History of participation in other clinical studies within 3 months or treatment with any gene therapy product.
• Intolerant or allergic to cyclophosphamide or fludarabine.
• Subjects not appropriate to participate in this clinical study judged by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LIGHT-PSMA-CART; Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -6 to -4. Patients receive LIGH-PSMA-CART IV at split doses from day 0 on.	Biological: LIGHT-PSMA-CART cells; LIGHT-PSMA-CART cells will be given IV at split doses; Other Names: Autologous PSMA-specific chimeric antigen cells co-expressing LIGHT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response rate	proportion of patients with ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4 weeks	24 weeks
Radiographic response rate by RECIST 1.1 & PCWG3.	Proportion of patients with a best response of either complete response or partial response, assessed using Prostate Cancer Working group3(PCWG3) response criteria &RECIST 1.1.	24 weeks
Duration time of CART cells in vivo	Number of persistent PSMA-CART cells detected by Q-PCR or flow cytometry	24 weeks

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: Changhai Hospital
• Investigators: Principal Investigator: Shancheng Ren, Professor, Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): May 15, 2022
• Study Completion (Estimated): October 15, 2024

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Castrate-Resistant
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2020-CAR-00CH1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No