Study of ORIC-944 in Patients With Metastatic Prostate Cancer

NCT ID: NCT05413421

Last Updated: 2025-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-01

Study Completion Date

2026-09-30

Brief Summary

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The purpose of this study is to establish the safety and preliminary antitumor activity of ORIC-944 as a single agent and in combinations with ARPIs in patients with metastatic prostate cancer.

Detailed Description

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ORIC-944 is a potent, highly selective, allosteric, orally bioavailable, small molecule inhibitor of PRC2 via binding the embryonic ectoderm development (EED) subunit.

This is a first-in-human, open-label, multicenter, dose escalation study of ORIC-944 as a single agent (Part I) or in combination with an Androgen Receptor Pathway Inhibitor (ARPI) (Part II) to establish the safety and preliminary antitumor activity of ORIC-944 as a single agent and in combination with ARPIs in patients with metastatic prostate cancer. Part III of the protocol (dose optimization) will explore two potential dose levels of ORIC-944 selected from Part II in combination with ARPIs to select the final RP2D for each combination across two separate patient populations.

Conditions

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Metastatic Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Interval 3+3 dose escalation design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Single Agent Dose Escalation

ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles

Group Type EXPERIMENTAL

ORIC-944

Intervention Type DRUG

Oral, once daily, continuous

Combination Dose Escalation

ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide

Group Type EXPERIMENTAL

ORIC-944

Intervention Type DRUG

Oral, once daily, continuous

Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets

Intervention Type DRUG

Oral, 1000 mg once daily, continuous

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Intervention Type DRUG

Oral, 240 mg once daily, continuous

Darolutamide (Nubeqa®) 300 mg tablets

Intervention Type DRUG

Oral, 600 mg twice daily, continuous

Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets

Intervention Type DRUG

Oral, 160 mg once daily, continuous

Combination Dose Optimization

Cohort A and C: ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combination with apalutamide

Cohort B and D: ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combination with darolutamide

Combinations with abiraterone or enzalutamide may be conducted in the future

Group Type EXPERIMENTAL

ORIC-944

Intervention Type DRUG

Oral, once daily, continuous

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Intervention Type DRUG

Oral, 240 mg once daily, continuous

Darolutamide (Nubeqa®) 300 mg tablets

Intervention Type DRUG

Oral, 600 mg twice daily, continuous

Interventions

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ORIC-944

Oral, once daily, continuous

Intervention Type DRUG

Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets

Oral, 1000 mg once daily, continuous

Intervention Type DRUG

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Oral, 240 mg once daily, continuous

Intervention Type DRUG

Darolutamide (Nubeqa®) 300 mg tablets

Oral, 600 mg twice daily, continuous

Intervention Type DRUG

Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets

Oral, 160 mg once daily, continuous

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with metastatic prostate cancer
* Must have undergone bilateral orchiectomy or be willing to continue GnRH analogue or antagonist to maintain castrate levels of testosterone
* Prior therapies:

Part I (single agent ORIC-944 dose escalation): Any number of prior therapies are allowed, but must have progressed after at least one line of next generation ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) and must not have received more than 2 chemotherapy regimens in the mCRPC setting

Part II (ARPI combination dose escalation): Must have received only 1 prior line of ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) in any setting; may have also received up to 1 prior line of chemotherapy in the mCSPC setting

Part III (ARPI combination dose optimization): In addition to up to 1 prior line of chemotherapy in the mCSPC setting:

* Cohorts A and B: received only one 1 prior line of abiraterone in any setting
* Cohorts C and D: received only one 1 prior line of apalutamide, darolutamide, or enzalutamide in any setting:

* Evidence of progressive disease by PCWG3 criteria for study entry

* rising PSA, defined as a minimum of 2 rising values obtained a minimum of one week apart with the latest result being at least 2.0 ng/mL (or 1.0 ng/mL if PSA rise is the only indication of progression), or
* confirmation of 2 new bone lesions on last systemic therapy, or
* soft tissue progression per RECIST 1.1
* Measurable and/or evaluable disease by RECIST 1.1
* Agreement and ability to undergo on-study punch skin biopsies and core tumor biopsies
* ECOG performance status of 0 or 1
* Adequate organ function

Exclusion Criteria

* History or presence of CNS metastases, unless previously treated and stable
* History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
* Known, symptomatic human immunodeficiency virus (HIV) infection
* Active symptomatic Hepatitis B or C infection; patients with well controlled disease are eligible
* Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, short gut syndrome, etc) or other malabsorption syndromes that would reasonably impact drug absorption per investigator judgement
* Any other condition or circumstance (eg, clinical, psychological, familial, sociological, inability to swallow oral study drug) that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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ORIC Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pratik S. Multani, MD

Role: STUDY_DIRECTOR

ORIC Pharmaceuticals

Locations

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Rocky Mountain Cancer Center

Colorado Springs, Colorado, United States

Site Status RECRUITING

South Florida Oncology and Hematology

Plantation, Florida, United States

Site Status RECRUITING

Illinois Cancer Specialists

Arlington Heights, Illinois, United States

Site Status RECRUITING

Comprehensive Urologic Care

Lake Barrington, Illinois, United States

Site Status RECRUITING

First Urology

Jeffersonville, Indiana, United States

Site Status RECRUITING

Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Maryland Oncology Hematology

Silver Spring, Maryland, United States

Site Status RECRUITING

Karmanos

Detroit, Michigan, United States

Site Status RECRUITING

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

Site Status RECRUITING

Memorial Sloane Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

Keystone Urology Specialists

Lancaster, Pennsylvania, United States

Site Status RECRUITING

Amarillo Urology Research

Amarillo, Texas, United States

Site Status RECRUITING

Urology Clinics of North Texas

Dallas, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Oncology Associates

Fairfax, Virginia, United States

Site Status RECRUITING

Virginia Cancer Specialists

Norfolk, Virginia, United States

Site Status NOT_YET_RECRUITING

University of Washington, Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status NOT_YET_RECRUITING

Sydney Adventist Health

Wahroonga, New South Wales, Australia

Site Status RECRUITING

Bendigo Health

Bendigo, Victoria, Australia

Site Status RECRUITING

Peninsula Health

Frankston, Victoria, Australia

Site Status NOT_YET_RECRUITING

NEXT Oncology

Barcelona, Barcelona, Spain

Site Status RECRUITING

Vall d'Hebron Institute of Oncology

Barcelona, Barcelona, Spain

Site Status RECRUITING

NEXT Oncology

Madrid, , Spain

Site Status RECRUITING

Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Site Status RECRUITING

Countries

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United States Australia Spain United Kingdom

Central Contacts

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ORIC Clinical

Role: CONTACT

650-388-5600

Other Identifiers

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ORIC-944-01

Identifier Type: -

Identifier Source: org_study_id

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