Recruiting
Phase 1

ORIC-944

Sponsor:

ORIC Pharmaceuticals

Code:

NCT05413421

Conditions

Metastatic Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ORIC-944

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

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Darolutamide (Nubeqa®) 300 mg tablets

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

Study Details

Brief summary:

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.

Conditions

Metastatic Prostate Cancer

Study ID

NCT05413421

Start date

Jun 1, 2022

Status verified date

Jul, 2026

Completion date

Apr, 2028

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

275 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Single Agent Dose Escalation

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

experimental: 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

experimental: 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

Interventions

ORIC-944

Oral, once daily, continuous

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

Oral, 1000 mg once daily, continuous

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Oral, 240 mg once daily, continuous

Darolutamide (Nubeqa®) 300 mg tablets

Oral, 600 mg twice daily, continuous

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

Oral, 160 mg once daily, continuous

Primary outcome measure

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
  • Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
  • Time to maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
  • Area under the curve (AUC) [ Time Frame: 28 Days ]
  • Apparent plasma terminal elimination half-life (t1/2) [ Time Frame: 28 Days ]

Central Contacts and Locations

Central contacts

ORIC Clinical

650-388-5600clinical@oricpharma.com

Locations

Rocky Mountain Cancer Center

Recruiting

Colorado Springs, Colorado, United States, 80907

South Florida Oncology and Hematology

Recruiting

Plantation, Florida, United States, 33322

Illinois Cancer Specialists

Recruiting

Arlington Heights, Illinois, United States, 60005

Comprehensive Urologic Care

Recruiting

Lake Barrington, Illinois, United States, 60010

First Urology

Recruiting

Jeffersonville, Indiana, United States, 47130

Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland

Recruiting

Baltimore, Maryland, United States, 21201

Maryland Oncology Hematology

Recruiting

Silver Spring, Maryland, United States, 20904

Karmanos

Recruiting

Detroit, Michigan, United States, 48201

Minnesota Oncology Hematology

Recruiting

Minneapolis, Minnesota, United States, 55404

Memorial Sloane Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Keystone Urology Specialists

Recruiting

Lancaster, Pennsylvania, United States, 17601

Amarillo Urology Research

Recruiting

Amarillo, Texas, United States, 74035

Urology Clinics of North Texas

Recruiting

Dallas, Texas, United States, 75231

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Virginia Oncology Associates

Recruiting

Fairfax, Virginia, United States, 22031

University of Washington, Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

More Information

Sponsor

ORIC Pharmaceuticals

Last update posted

Jul 9, 2026

Last verified

Jul, 2026

Keywords

  • PRC2 dysregulation
  • EED
  • CRPC
  • mCRPC
  • ARPI

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by ORIC Pharmaceuticals on 2026-07-09.