PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer

Metastatic Prostate Carcinoma Clinical Trial

Official title: A Phase 1b Study Evaluating Combinations With PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer

Status Recruiting

Clinical Trial Summary

This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor (CAR)-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes (PSCA-CAR T cells), plus or minus radiation, in treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Castration-resistant prostate cancer continues to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving PSCA-targeting CAR T-cells, with or without radiation, may kill more tumor cells in men with castration-resistant prostate cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. Assess the feasibility, safety, and activity of lymphodepleting chemotherapy followed by up to 3 cycles of 50M PSCA-CAR T cell immunotherapy per course either alone (treatment plan 1 [TP1]) or in combination with metastasis-directed radiation therapy (MDRT) (treatment plan 2 [TP2]) in adult patients with metastatic castration-resistant prostate cancer (mCRPC).

SECONDARY OBJECTIVES:

I. Describe persistence and expansion of CAR T cells in peripheral blood (PB). II. Describe cytokine levels over the study period. III. Estimate disease response rates. IV. Estimate 6-month progression-free survival (PFS) rate. V. Estimate 1-year overall survival (OS) rate.

EXPLORATORY OBJECTIVES:

I. Describe the immune landscape changes in PB and tumors. II. Describe phenotype of CAR T cells in PB. III. Describe tumor evolution in PB (circulating tumor cells [CTCs], circulating cell-free deoxyribonucleic acid [DNA] [cfDNA]) and tumors.

IV. Determine whether urine cytokines and cellularity is predictive of cystitis occurrence/severity.

V. Analyze microbial changes in stool associated with CAR T cell therapy.

OUTLINE: Patients are assigned to 1 of 2 treatment plans.

TREATMENT PLAN I: Patients undergo leukapheresis and lymphodepletion and receive PSCA-CAR T cells intravenously (IV) up to 3 times on study.

TREATMENT PLAN II: Patients undergo leukapheresis, radiation in 2 doses, and lymphodepletion, and receive PSCA-CAR T cells IV up to 3 times on study.

Patients in both arms undergo bone scan, computed tomography (CT) scan, tumor biopsy, and collection of blood, stool and urine samples throughout the trial. ;

Related Conditions & MeSH terms

• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Prostatic Neoplasms
• Stage IVB Prostate Cancer AJCC v8

• NCT number: NCT05805371
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 1
• Start date: June 12, 2024
• Completion date: July 1, 2028