NCT07723248

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for phase_3

Timeline
50mo left

Started Jul 2026

Typical duration for phase_3

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress2%
Jul 2026Sep 2030

First Submitted

Initial submission to the registry

June 18, 2026

Completed
13 days until next milestone

Study Start

First participant enrolled

July 1, 2026

Completed
22 days until next milestone

First Posted

Study publicly available on registry

July 23, 2026

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2030

Last Updated

July 23, 2026

Status Verified

July 1, 2026

Enrollment Period

1.7 years

First QC Date

June 18, 2026

Last Update Submit

July 20, 2026

Conditions

Keywords

prostate canceradvanced prostate cancerhormone dependent malignancyhormone resistantrelapsedrefractoryandrogen receptor (AR) signalingmetastatic castration resistant prostate cancer (mCRPC)androgen pathway modulator-resistant (APMR)metastatic castration sensitive prostate cancer (mCSPC)androgen pathway modulator-naïve/sensitive (APMN/S)polycomb repressive complex 2 (PRC2)-controlled dysregulationembryonic ectoderm development (EED)enhancer of zeste homolog 2 (EZH2)ORIC-944rinzimetostatmevrometostatdarolutamideenzalutamidedocetaxelabirateroneabiraterone acetateefficacysafetyopen-label

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (21)

  • Overall Survival (OS)

    5 years

  • Objective response rate (ORR)

    Randomization up to ~2 years

  • Duration of Response (DoR)

    Randomization up to ~2 years

  • Prostate Specific Antigen (PSA) response

    Randomization up to ~2 years

  • Time to PSA progression

    Randomization up to ~2 years

  • +16 more secondary outcomes

Study Arms (2)

Investigational Arm

ACTIVE COMPARATOR

Rinzimetostat + darolutamide

Drug: RinzimetostatDrug: Darolutamide

Physician's Choice

ACTIVE COMPARATOR

Control Arm

Drug: DarolutamideDrug: EnzalutamideDrug: Docetaxel

Interventions

400 mg once daily (QD)

Also known as: ORIC-944
Investigational Arm

600 mg twice daily (BID)

Also known as: Nubeqa
Investigational ArmPhysician's Choice

160 mg once daily (QD)

Also known as: Xtandi
Physician's Choice

75 mg/m2 intravenously (IV) every 21 days for up to 10 cycles

Also known as: Taxotere
Physician's Choice

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Urology Specialists of the Carolinas - University Place

Charlotte, North Carolina, 29464, United States

RECRUITING

Summit Urology

Murray, Utah, 84107, United States

RECRUITING

MeSH Terms

Conditions

Prostatic NeoplasmsRecurrenceBulbo-Spinal Atrophy, X-Linked

Interventions

darolutamideenzalutamideDocetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsMuscular Atrophy, SpinalSpinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesMotor Neuron DiseaseNeuromuscular DiseasesGenetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Central Study Contacts

ORIC Clinical Call Center

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 18, 2026

First Posted

July 23, 2026

Study Start

July 1, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

September 1, 2030

Last Updated

July 23, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will not share

Locations