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

NCT05805371 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22378NCI-2023-02186P30CA033572
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Dose limiting toxicities (DLTs), cystitis, grade 3 toxicities and the full toxicity profile as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and cytokine release syndrome (CRS) and neurotoxicity as assessed by modified CRS grading. The recommended phase 2 dose (RP2D) will be based on the treatment plan 2 toxicity, activity and correlative data. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for DLTs within the DLT period. Tables will be created to summarize all toxicities and side effects by attribution to treatment arm, dose, organ and severity.

  Post chimeric antigen receptor (CAR) T cell infusion up to 15 years

• 50% prostate specific antigen (PSA) level reduction

  Statistical and graphical methods will be used to describe cytokine levels (peripheral blood) and PSA levels over the study period.

  From baseline measurement up to 1 year post study treatment

Secondary Outcomes (9)

• Persistence of CAR T cells

  Up to 28 days post last study treatment

• Expansion of CAR T cells

  Up to 28 days post last study treatment

• PSCA tumor expression

  From baseline to end of cycle 1 (Cycle length is 56 days)

• Serum cytokine profile

  Before CAR T cell infusion through completion of cycle 2, up to 4 months (Cycle length is 56 days)

• Overall survival

  From time of lymphodepletion to date of death, assessed at 1 year

Study Arms (2)

Treatment plan I (PSCA CAR T-cells)

EXPERIMENTAL

Patients undergo leukapheresis and lymphodepletion and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.

Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Lymphodepletion Therapy

Treatment plan II (PSCA CAR T-cells, radiation)

EXPERIMENTAL

Patients undergo leukapheresis, radiation in 2 doses, and lymphodepletion, and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.

Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Procedure: Leukapheresis; Procedure: Lymphodepletion Therapy

Interventions

Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes BIOLOGICAL

Given IV

Also known as: Autologous Anti-PSCA(dCH2)BBz-CAR T-cells, Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-cells, PSCA(dCH2)BBzeta-CAR T-cells

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Biospecimen Collection PROCEDURE

Undergo blood, stool, and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

External Beam Radiation Therapy RADIATION

Undergo radiation

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Treatment plan II (PSCA CAR T-cells, radiation)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Lymphodepletion Therapy PROCEDURE

Undergo lymphodepletion

Also known as: Lymphodepleting Therapy, Lymphodepletion

Treatment plan I (PSCA CAR T-cells); Treatment plan II (PSCA CAR T-cells, radiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative (brown)
• Assent, when appropriate, will be obtained per institutional guidelines
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with lymphodepletion and CAR T cell infusion only after the translated main consent form is signed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky Performance Status (KPS) \>= 70%
• Documented castration resistant prostate cancer (mCRPC) (Note: castration will be defined by a testosterone \< 50 ng/dL achieved by orchiectomy or luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist therapy)
• Documented PSCA+ tumor expression as evaluated by the COH Pathology Clinical Trials Specimen Qualification Laboratory (CTSQL)
• Fresh or archival biopsy samples may be tested for PSCA expression during screening for eligibility purposes. The results from soft tissue biopsies will be used to confirm eligibility for participants who have a soft-tissue lesion biopsy obtained, but bone biopsy staining results will not impact eligibility since immunohistochemistry (IHC) staining for PSCA has not been optimized in bone specimens. Subjects who undergo bone biopsy on study will be qualified based on the archival tissue result
• Progression of disease manifest by one of the following means during treatment with at least one advanced androgen targeted therapy (e.g., abiraterone or enzalutamide):
• Rising prostate specific antigen (PSA) documented on 2 occasions at least 7 days apart, with absolute increase \> 2 ng/dL despite testosterone \< 50 OR
• Radiographic evidence of new metastatic foci on CT or bone scan, or soft tissue progression by Response Evaluation Criteria in Solid Tumors (RECIST)
• For treatment plan 2, subjects must have at least one and up to 3 metastatic lesions which have not previously been radiated and which is safe for treatment with radiation 16 gray (Gy) in 2 fractions
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy

You may not qualify if:

• Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
• Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to screening
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for \>= 3 years
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Biopsy; Specimen Handling; Radiation; Leukapheresis

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Physical Phenomena; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation

Study Officials

• Tanya B Dorff

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 10, 2023
• Study Start: July 19, 2024
• Primary Completion (Estimated): November 11, 2028
• Study Completion (Estimated): November 11, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

US (1)