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

Official title

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)

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

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

United States · 2 centers

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗