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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: Rinzimetostat; Drug: Darolutamide; Drug: Enzalutamide; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ORIC Clinical Call Center; Email: clinical@oricpharma.com

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 29464
      • Recruiting
      • Urology Specialists of the Carolinas - University Place
      • Principal Investigator: Jeremy Hubbard, MD
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Summit Urology
      • Principal Investigator: Stewart Landau, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. Treatment with first-generation antiandrogen agents (eg, bicalutamide, flutamide, nilutamide), but must be discontinued prior to the first dose of study medication
  2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Investigational Arm; Rinzimetostat + darolutamide	Drug: Rinzimetostat; 400 mg once daily (QD); Other Names: ORIC-944; Drug: Darolutamide; 600 mg twice daily (BID); Other Names: Nubeqa
Active Comparator: Physician's Choice; Control Arm	Drug: Darolutamide; 600 mg twice daily (BID); Other Names: Nubeqa; Drug: Enzalutamide; 160 mg once daily (QD); Other Names: Xtandi; Drug: Docetaxel; 75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression Free Survival assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)	Radiographic Progression Free Survival is defined as the time from the date of randomization to first evidence of radiographic progression as assessed in soft tissue by RECIST 1.1 or in bone per PCWG3 guideline by BICR, or death, whichever occurs first	Randomization up to ~2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as time from date of randomization to date of death due to any cause	5 years
Objective response rate (ORR)	ORR is defined as proportion of patients with measurable soft tissue disease at baseline who have a confirmed objective response of complete response (CR) or partial response (PR)	Randomization up to ~2 years
Duration of Response (DoR)	DOR is defined as time of first response to first documentation of radiographic progression or death, whichever occurs first	Randomization up to ~2 years
Prostate Specific Antigen (PSA) response	Defined as the proportion of patients with a confirmed ≥50% and ≥90% decline in PSA from baseline as per the PCWG3 criteria, along with the maximum decline in PSA occurring at any point on study	Randomization up to ~2 years
Time to PSA progression	Measured from the start of treatment until criteria for PSA progression are met as per PCWG3	Randomization up to ~2 years
Time to initiation of antineoplastic therapy	Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)	Randomization up to ~4 years
Time to first symptomatic skeletal event	Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first) Compare patient reported outcomes (PROs) between the investigational treatment and control arms	Randomization up to ~4 years
Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)	Analysis of Brief Pain Inventory-Short Form (BPI-SF) will be based on the pain severity score (mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (the mean of items 9A-9G), and the single BPI-SF Item 3 which asks the patient to rate pain at its worst in the last 24 hours	Randomization up to ~4 years
Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Change from baseline in HRQoL (FACT-P total score) will be presented. The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire. Each item is rated on a 0 to 4 Likert-type scale and then combined to produce the FACT-P total score (0-156), with higher scores representing better health-related quality of life	Randomization up to ~4 years
Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Change from baseline in social/family well-being score will be presented. The social/family well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale	Randomization up to ~4 years
Change from baseline in functioning well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Change from baseline in functioning well-being score will be presented. The functioning well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale	Randomization up to ~4 years
Change from baseline in physical well-being per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Change from baseline in physical well-being score will be presented. The physical well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale	Randomization up to ~4 years
Change from baseline in symptoms per Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Change from baseline prostate cancer symptoms (PCS) score will be presented. The PCS score will be calculated based on 12 items in the FACT-P questionnaire; score range 0-48. Each item is rated on a 0 to 4 Likert-type scale	Randomization up to ~4 years
Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)	Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension. The questionnaire also includes a visual analog scale to self-rate general health state on a scale from "the worst health you can imagine" to "the best health you can imagine."	Randomization up to ~4 years
Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)	Each selected PRO-CTCAE items will be assessed related to one or more attributes that include counts for the frequency, severity, and/or interference with usual or daily activities	Randomization up to ~2 years
Overall side effect burden as measured by the FACT- GP5	The FACT-GP5 question assesses overall side effect burden with the following response options "I am bothered by side effects of treatment," is rated on a 5-point scale ranging from "not at all" (0) to "very much" (4) and counts will be presented	Randomization up to ~2 years
Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours"	Defined as the time from randomization to onset of pain progression, which is defined as > 2-point increase from baseline in the score from the BPI-SF Question 3 that is confirmed at the next consecutive assessment > 4 weeks apart or an initial deterioration followed by death before the next assessment	Randomization up to ~4 years
Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P	Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as >10 point decrease from baseline and no subsequent observations with a <10 point decrease from baseline FACT-P total score	Randomization up to ~4 years
Time to definitive deterioration in patient-reported physical well-being per FACT-P	Time to definitive deterioration in physical well-being (PWB) per FACT-P is defined as the time from randomization to onset of definitive deterioration in physical well-being, which is defined as ≥3-point	Randomization up to ~4 years
Incidence of Adverse Events (AEs)	Type, incidence, relationship to study treatments, severity, and seriousness of AEs [as graded by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v6.0] and other clinical assessments	Randomization up to ~2 years
Evaluate the pharmacokinetics (PK) of rinzimetostat in combination with darolutamide	Rinzimetostat characterized by predose and postdose plasma concentrations at selected time points	Randomization up to ~1 year

Collaborators and Investigators

• Sponsor: ORIC Pharmaceuticals
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: safety; prostate cancer; open-label; efficacy; enzalutamide; abiraterone; relapsed; refractory; advanced prostate cancer; docetaxel; hormone resistant; abiraterone acetate; darolutamide; metastatic castration resistant prostate cancer (mCRPC); hormone dependent malignancy; androgen receptor (AR) signaling; androgen pathway modulator-resistant (APMR); metastatic castration sensitive prostate cancer (mCSPC); androgen pathway modulator-naïve/sensitive (APMN/S); polycomb repressive complex 2 (PRC2)-controlled dysregulation; embryonic ectoderm development (EED); enhancer of zeste homolog 2 (EZH2); ORIC-944; rinzimetostat; mevrometostat
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neuromuscular Diseases; Disease Attributes; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Recurrence; Bulbo-Spinal Atrophy, X-Linked; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; darolutamide; enzalutamide
• Other Study ID Numbers: ORIC-944-05; 2026-525340-15-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No