A Phase III Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer

NCT07311694 | Recruiting Phase 3

• 1 other identifier: HRS-4357-301
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, open-label, controlled, multicenter phase III clinical trial, which plans to randomly enroll 370 subjects with advanced metastatic castration-resistant prostate cancer (mCRPC). The efficacy of HRS-4357 versus novel androgen receptor pathway inhibitors (ARPI) in the treatment of PSMA-positive advanced metastatic castration-resistant prostate cancer (mCRPC) will be evaluated based on radiographic progression-free survival (rPFS) assessed by the BIRC.

Conditions

PSMA-Positive Progressive Metastatic Castration-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• radiographic progression-free survival (rPFS) assessed by the BIRC.

  From Baseline to primary completion date, about 24 months

Secondary Outcomes (11)

• OS

  From Baseline to primary completion date, about 24 months

• rPFS（Investigator-Assessed）

  From Baseline to primary completion date, about 24 months

• ORR （Investigator-Assessed and BIRC-Assessed）

  From Baseline to primary completion date, about 24 months

• DCR（Investigator-Assessed and BIRC-Assessed）

  From Baseline to primary completion date, about 24 months

• DOR（Investigator-Assessed and BIRC-Assessed）

  From Baseline to primary completion date, about 24 months

Study Arms (2)

HRS-4357 injection

EXPERIMENTAL

Drug: HRS-4357 injection

Enzalutamide Soft Capsules / Abiraterone Acetate Tablets+ Prednisone Acetate Tablets

ACTIVE COMPARATOR

Drug: Enzalutamide；Abiraterone

Interventions

HRS-4357 injection DRUG

HRS-4357 injection are administered each time, with dosing for 4 to 6 cycles

HRS-4357 injection

Enzalutamide；Abiraterone DRUG

ARPI (investigator's choice of any of the following agents, with the requirement that the agent has not been used previously): * Enzalutamide 160 mg orally once daily (qd) * Abiraterone 1000 mg orally once daily (qd) + Prednisone 5 mg orally twice daily (bid)

Enzalutamide Soft Capsules / Abiraterone Acetate Tablets+ Prednisone Acetate Tablets

Eligibility Criteria

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

You may qualify if:

• Be willing to participate in this clinical trial, understand the study procedures, and be able to sign the informed consent form in writing;
• Male, aged ≥ 18 years;
• ECOG performance status score of 0-1;
• Expected survival time of no less than 6 months;
• Prostate adenocarcinoma confirmed by histology and/or cytology, and diagnosed as mCRPC (metastatic castration-resistant prostate cancer) with reference to current clinical guidelines;
• Presence of at least one metastatic lesion confirmed by imaging examinations (CT/MRI and/or bone scan) within 4 weeks before randomization;
• Confirmation of at least one PSMA-positive lesion and no PSMA-negative lesions by PSMA PET/CT;
• Serum testosterone at castration level (\< 50 ng/dl or \< 1.7 nmol/L) at the screening visit; continuous luteinizing hormone-releasing hormone analog (LHRHA) therapy (medical castration) or previous bilateral orchiectomy (surgical castration); subjects who have not undergone bilateral orchiectomy must plan to maintain effective LHRHA therapy throughout the study period;
• Previous treatment with second-generation ARPIs, with only one episode of disease progression during treatment; and assessed by the investigator as suitable for switching to another ARPI (suitable for receiving abiraterone or enzalutamide);
• Disease progression at the time of enrollment. Disease progression is defined as the occurrence of at least one of the following while the subject's serum testosterone is at a stable castration level: ① PSA progression: PSA value \> 1 ng/mL, with two consecutive increases in PSA at intervals of at least 1 week; ② Radiographic progression: occurrence of clearly new lesions; appearance of 2 or more new bone lesions on bone scan; lesion progression indicated by CT or MRI (per RECIST v1.1);

You may not qualify if:

• Received any of the following treatments before randomization:
• Any radionuclide therapy or hemi-body radiotherapy within 6 months.
• Any PSMA-targeted radiopharmaceutical therapy.
• Surgery, radiotherapy, or any local therapy within 4 weeks.
• Any other investigational drug intervention within 4 weeks.
• Known hypersensitivity to the components of the study drug or its analogs.
• History of malignancy (other than prostate cancer) within 5 years before randomization that is expected to alter life expectancy or may interfere with disease assessment, excluding cured malignancies with low risk of metastasis and mortality (5-year survival rate \> 90%), such as non-metastatic basal cell carcinoma of the skin, superficial squamous cell carcinoma of the skin, and low-grade superficial bladder cancer.
• Occurrence of severe infection (CTCAE \> Grade 2) within 4 weeks before randomization.
• Failure to recover from adverse events of previous treatments (NCI-CTCAE Version 5.0 Grade \> 1) before randomization, as judged by the investigator.
• Presence of poorly controlled clinical cardiac symptoms or cardiac diseases.
• History of physical or psychiatric illnesses/conditions that may interfere with the study objectives and assessments (including epilepsy and dementia).

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

Central Study Contacts

Yuezheng Ti

CONTACT

+0518-82342973; yuezheng.ti@hengrui.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: December 31, 2025
• Study Start: February 2, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 4, 2026

Record last verified: 2025-12

Locations

CN (1)