A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)

Официальное название

A Phase 3, Randomized, Open-Label Study of Rinzimetostat (ORIC-944) in Combination With Darolutamide Compared With ARPI or Docetaxel in Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Abiraterone Acetate (Himalayas-1)

Обзор

Himalayas-1 is a randomized, open-label, global, multicenter phase 3 study evaluating whether the combination of rinzimetostat with darolutamide is more effective compared to physician's choice of control; ARPI (darolutamide or enzalutamide) or docetaxel for treating patients with metastatic castration resistant prostate cancer (mCRPC) who were previously treated with abiraterone acetate. The primary objective of this study is to demonstrate superiority in radiographic progression free survival (rPFS) of the investigational arm of rinzimetostat + darolutamide combination versus physician's choice of control: ARPI (darolutamide or enzalutamide) or docetaxel.

Вмешательства

• Препарат Rinzimetostat
  400 mg once daily (QD)
• Препарат Darolutamide
  600 mg twice daily (BID)
• Препарат Enzalutamide
  160 mg once daily (QD)
• Препарат Docetaxel
  75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles

Первичные конечные точки

• Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) [Срок оценки: Randomization up to ~2 years]

Вторичные конечные точки (12)

• Overall Survival (OS) [Срок оценки: 5 years]
• Objective response rate (ORR) [Срок оценки: Randomization up to ~2 years]
• Duration of Response (DoR) [Срок оценки: Randomization up to ~2 years]
• Prostate Specific Antigen (PSA) response [Срок оценки: Randomization up to ~2 years]
• Time to PSA progression [Срок оценки: Randomization up to ~2 years]
• Time to initiation of antineoplastic therapy [Срок оценки: Randomization up to ~4 years]
• Time to first symptomatic skeletal event [Срок оценки: Randomization up to ~4 years]
• Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF) [Срок оценки: Randomization up to ~4 years]
• Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P) [Срок оценки: Randomization up to ~4 years]
• Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P) [Срок оценки: Randomization up to ~4 years]
• Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P) [Срок оценки: Randomization up to ~4 years]
• Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P) [Срок оценки: Randomization up to ~4 years]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features
• Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line mCRPC setting is required
• Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

Критерии исключения

• Prior treatment for prostate cancer at any stage with cytotoxic chemotherapy, radioligand therapy (ie, 177Lu -PSMA-617, radium-223), ARPIs including apalutamide, darolutamide, and enzalutamide, PARP monotherapy or other systemic anticancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene or cell therapy, angiogenesis inhibitors, CDK4/6 inhibitors, PRC2 inhibitors) with the following exceptions:

• Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
• Docetaxel treatment is allowed for mCSPC, as long as no signs of failure or disease progression occurred during treatment or within 3 months of treatment completion
• Any other anticancer therapy (drug or vaccine which does not meet exclusion criterion 1 above) within 28 days or 5 half-lives (whichever is longer) prior to randomization
• Known or suspected brain metastasis or active leptomeningeal disease
• Clinically significant cardiovascular disease defined as:
• Any medical (including active or clinically significant bacterial, fungal, or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the patient inappropriate for the study
• Active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery are excluded

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

США · 2 центра

• Urology Specialists of the Carolinas - University Place — Charlotte
• Summit Urology — Murray

Идентификаторы

NCT: NCT07723248 · ORIC-944-05 · 2026-525340-15-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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