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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

• 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);

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07311694 · HRS-4357-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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