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

Official title

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

Overview

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.

Interventions

• Drug HRS-4357 injection
  HRS-4357 injection are administered each time, with dosing for 4 to 6 cycles
• Drug Enzalutamide；Abiraterone
  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)

Primary outcome measures

• radiographic progression-free survival (rPFS) assessed by the BIRC. [Time frame: From Baseline to primary completion date, about 24 months]

Secondary outcome measures (11)

• OS [Time frame: From Baseline to primary completion date, about 24 months]
• rPFS（Investigator-Assessed） [Time frame: From Baseline to primary completion date, about 24 months]
• ORR （Investigator-Assessed and BIRC-Assessed） [Time frame: From Baseline to primary completion date, about 24 months]
• DCR（Investigator-Assessed and BIRC-Assessed） [Time frame: From Baseline to primary completion date, about 24 months]
• DOR（Investigator-Assessed and BIRC-Assessed） [Time frame: From Baseline to primary completion date, about 24 months]
• PSA50 Response Rate [Time frame: From Baseline to primary completion date, about 24 months]
• Time to PSA Progression [Time frame: From Baseline to primary completion date, about 24 months]
• Changes from baseline in scores of the EQ-5D-5L [Time frame: From Baseline to primary completion date, about 24 months]
• Changes from baseline in scores of the Functional FACT-P [Time frame: From Baseline to primary completion date, about 24 months]
• Changes from baseline in scores of the BPI-SF [Time frame: From Baseline to primary completion date, about 24 months]
• Assessment of the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Time frame: From Baseline to primary completion date, about 24 months]

Eligibility criteria

Inclusion criteria

• 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);

Exclusion criteria

• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07311694 · HRS-4357-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗