A Phase I Trial of A-CAR032 in Participants With mCRPC

First Time-in-Human (FTiH), Phase I Trial to Evaluate the Safety, Cellular Kinetics, and Efficacy of A-CAR032, in Adult Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This FTiH, single-arm, open-label, investigator-initiated Phase I trial will evaluate the safety, antitumour activity, CK/pharmacodynamics (PD), biomarkers, immunogenicity, and feasibility of A-CAR032 in adult participants with mCRPC, who have previously progressed after ARPI treatment of prostate cancer (whether before or in the metastatic castration-resistant setting) and, in the judgment of the investigator, are ineligible for standard treatment.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Biological: dnTGFβRII-armoured STEAP2-targeted autologous CAR T-Cell Injection

Detailed Description

The study consists of two parts: Part 1-Dose Escalation and Part 2-Dose Expansion. Participants in the study will proceed through screening, apheresis, bridging therapy (if appropriate), lymphodepletion, CAR-T cell infusion, and subsequent follow-up (including Stage 1, 2 and 3).

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Andy Zou; Phone Number: +86-21-54069990; Email: andy.zou@abelzeta.com
• Study Contact Backup: Name: Nicole Shen; Phone Number: +86-21-54069993; Email: yinghua.shen@abelzeta.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Xi-Nan Sheng; Phone Number: +86-10-88121122; Email: xinan.sheng@bjcancer.org
    • Beijing, Beijing Municipality, China, 102200
      • Not yet recruiting
      • Beijing GoBroad Hospital
      • Contact: Xieqiao Yan; Phone Number: +86-13581535150; Email: sedah1984@163.com
  • Hubei
    • Wuhan, Hubei, China, 430100
      • Recruiting
      • Tongji Hospital, Tongji Medical College of HUST
      • Contact: Bo Liu; Phone Number: +86-27-83663298; Email: boliu888@hotmail.com
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221006
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Zhengxiang Han; Phone Number: +86-516-85802000; Email: cnhzxyq@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310013
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Weijia Fang; Phone Number: +86-571-87236666; Email: weijiafang@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be 18 years or older at the time of signing the ICF. Type of Participant and Disease Characteristics

2. Participants with:

   1. A histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate without known neuroendocrine differentiation or small cell features.
   2. Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone analogue. Participants receiving medical castration therapy with gonadotropin-releasing hormone analogues should continue this treatment during the study.
   3. Measurable PSA≥1 ng/mL AND
   4. Evidence of progression within 6 months prior to screening
3. Participant has previously received an ARPI (ie, abiraterone, enzalutamide, apalutamide, darolutamide, rezvilutamide) whether before or in the metastatic castration-resistant setting, and in the judgment of the investigator, be ineligible for standard treatment.
4. Minimum life expectancy of > 12 weeks prior to apheresis in the opinion of the investigator.
5. Adequate organ and marrow function
6. Consent and provision of tumour material to assess STEAP2 expression and other correlative biomarkers retrospectively with pre- and post-treatment biopsies.
7. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. The participant voluntarily participates in the study, and the individual or their legal guardian signs the ICF.

Exclusion Criteria:

1. Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO).
2. Contraindication to lymphodepleting agents, including fludarabine and/or cyclophosphamide.

3. History of another primary malignancy except for:

   1. Malignancy treated with curative intent and with no known active disease within 3 years before the apheresis and of low potential risk for recurrence.
   2. Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease.
   3. Adequately treated carcinoma in situ without evidence of disease.
4. Participants with known brain metastases.
5. History of splenectomy or organ transplantation.

6. Prior treatment with:

   1. Any CAR-T therapy. OR
   2. Any therapy that is targeting STEAP2.
7. Active or prior documented autoimmune or inflammatory disorders
8. Cardiac arrhythmias which are symptomatic or require treatment unless controlled by pacemaker (judged by investigator); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.

9. Active infection, including:

   1. HBV infection is defined as hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and HBV DNA detectable.
   2. HCV infection is defined as HCV antibody positive and HCV RNA positive.
   3. CMV infection is defined as CMV DNA detectable.
   4. Syphilis infection is defined as syphilis antigen and antibody positive.
   5. HIV infection is defined as HIV 1/2 antibody positive.
   6. Other persistent or active infections requiring systemic treatment (prophylactic use of anti-infective drugs is allowed).
10. Patients with central nervous system (CNS) diseases:
11. Obvious risk or tendency of bleeding or active bleeding (eg, clinically significant hemoptysis, tumour bleeding, history of von Willebrand disease or hemophilia etc.).
12. Plans to father a child during the study period.
13. Patients with alcohol or drug abuse.
14. Participants may not receive full-dose long acting oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose from the time of informed consent to 28 days post infusion of A-CAR032. Use of short acting direct oral anticoagulants for therapeutic and prophylactic purposes are permitted.

15. Received the following:

    1. Major surgery within 4 weeks prior to apheresis or existence of unhealed wound, or planned major surgery within 4 weeks of the study treatment administration
    2. Steroids (except inhaled steroids) or other immunomodulators (including interleukins, interferons, and thymosins) of systemic therapeutic dose, and systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent within 5 half-lives or 7 days (whichever is shorter) prior to apheresis.
16. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies, investigational product) within 5 half-lives or ≤ 21 days (whichever is shorter) prior to apheresis.
17. Radiotherapy within 4 weeks of apheresis (However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the participant is eligible irrespective of the end date of radiotherapy); or within 6 months or 5 half-lives (whichever is longer) if local radioactive particle implantation was performed.

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: A-CAR032; Part 1 will follow an i3+3 design which is employed to explore the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE). Three dose levels of A-CAR032are initially planned with a minimum of 3 and maximum of 9 participants per dose level. The safety review committee (SRC) may suggest exploration of intermediate dose levels or additional higher or lower dose levels based on the available data, but will not exceed 3 times the current dose or 3 times the highest dose that has been determined safe by the SRC.Part 2 at the RDE of A-CAR032 will be initiated, if data support, to further evaluate the safety, CK, efficacy and potential biological activity of study intervention. Approximately 12 evaluable participants will be enrolled in Part 2.

Biological: dnTGFβRII-armoured STEAP2-targeted autologous CAR T-Cell Injection; dnTGFβRII-armoured STEAP2-targeted autologous CAR T-Cell Injection.single infusion intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation (Part 1)：Safety	Incidence of AEs/SAEs	From ICF signature until 15 years post A-CAR032 infusion
Dose Escalation (Part 1)：Safety	Occurrence of DLTs/DLT-like events	Throughout the 28 days post A-CAR032 infusion
Dose Escalation (Part 1)：Safety	Changes from baseline in laboratory parameters, vital signs, and ECGs	From ICF signature until 12 months post A-CAR032 infusion
Dose Expansion (Part 2)：Safety	Incidence of AEs/SAEs	From ICF signature until 15 years post A-CAR032 infusion
Dose Expansion (Part 2)：Safety	Incidence of DLT-like events	Throughout the 28 days post A-CAR032 infusion
Dose Expansion (Part 2)：Safety	Changes from baseline in laboratory parameters, vital signs, and ECGs	From ICF signature until 12 months post A-CAR032 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy	PSA-related response	From ICF signature until 12 months post A-CAR032 infusion
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy	Radiological response	From ICF signature until 12 months post A-CAR032 infusion
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy	rPFS	From ICF signature until 12 months post A-CAR032 infusion
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy	OS	From ICF signature until 15 years post A-CAR032 infusion
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy	Time from A-CAR032 infusion to first SSRE	From A-CAR032 infusion until 12 months post A-CAR032 infusion
Dose Escalation (Part 1) and Dose Expansion (Part 2)：Pharmacokinetics	CK profile of A-CAR032	From ICF signature until 15 years post A-CAR032 infusion

Collaborators and Investigators

• Sponsor: Shanghai AbelZeta Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2042

Study Registration Dates

• First Submitted: January 7, 2026
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 1332-046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No