Study of ORIC-944 in Patients With Metastatic Prostate Cancer

NCT05413421 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ORIC-944-01
• Study Type: interventional
• Target: 250
• Locations: 4 countries
• Sites: 27

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

Keywords

PRC2 dysregulation; EED; CRPC; mCRPC; ARPI

Outcome Measures

Primary Outcomes (5)

• Recommended Phase 2 Dose (RP2D)

  RP2D as determined by interval 3+3 dose escalation design

  12 months

• Maximum plasma concentration (Cmax)

  PK of ORIC-944 single agent and in combination with an ARPI

  28 Days

• Time to maximum observed concentration (Tmax)

  PK of ORIC-944 single agent and in combination with an ARPI

  28 Days

• Area under the curve (AUC)

  PK of ORIC-944 single agent and in combination with an ARPI

  28 Days

• Apparent plasma terminal elimination half-life (t1/2)

  PK of ORIC-944 single agent and in combination with an ARPI

  28 Days

Secondary Outcomes (5)

• Clinical benefit rate (CBR)

  36 months

• Objective response rate (ORR)

  36 months

• Duration of response (DOR)

  36 months

• Progression-free survival (PFS)

  36 months

• On-treatment PSA levels and change from baseline

  36 months

Study Arms (3)

Single Agent Dose Escalation

EXPERIMENTAL

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

Drug: ORIC-944

Combination Dose Escalation

EXPERIMENTAL

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

Drug: ORIC-944; Drug: Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets; Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Darolutamide (Nubeqa®) 300 mg tablets; Drug: Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets

Combination Dose Optimization

EXPERIMENTAL

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

Drug: ORIC-944; Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Darolutamide (Nubeqa®) 300 mg tablets

Interventions

ORIC-944 DRUG

Oral, once daily, continuous

Combination Dose Escalation; Combination Dose Optimization; Single Agent Dose Escalation

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

Oral, 1000 mg once daily, continuous

Combination Dose Escalation

Apalutamide (Erleada™) 60 mg or 240 mg tablets DRUG

Oral, 240 mg once daily, continuous

Combination Dose Escalation; Combination Dose Optimization

Darolutamide (Nubeqa®) 300 mg tablets DRUG

Oral, 600 mg twice daily, continuous

Combination Dose Escalation; Combination Dose Optimization

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

Oral, 160 mg once daily, continuous

Combination Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead

Study Sites (27)

Rocky Mountain Cancer Center

Colorado Springs, Colorado, 80907, United States

RECRUITING

South Florida Oncology and Hematology

Plantation, Florida, 33322, United States

RECRUITING

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

RECRUITING

Comprehensive Urologic Care

Lake Barrington, Illinois, 60010, United States

RECRUITING

First Urology

Jeffersonville, Indiana, 47130, United States

RECRUITING

Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

RECRUITING

Maryland Oncology Hematology

Silver Spring, Maryland, 20904, United States

RECRUITING

Karmanos

Detroit, Michigan, 48201, United States

RECRUITING

Minnesota Oncology Hematology

Minneapolis, Minnesota, 55404, United States

RECRUITING

Memorial Sloane Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

NOT YET RECRUITING

Keystone Urology Specialists

Lancaster, Pennsylvania, 17601, United States

RECRUITING

Amarillo Urology Research

Amarillo, Texas, 74035, United States

RECRUITING

Urology Clinics of North Texas

Dallas, Texas, 75231, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Virginia Oncology Associates

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Cancer Specialists

Norfolk, Virginia, 23502, United States

NOT YET RECRUITING

University of Washington, Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

NOT YET RECRUITING

Sydney Adventist Health

Wahroonga, New South Wales, Australia

RECRUITING

Bendigo Health

Bendigo, Victoria, Australia

RECRUITING

Peninsula Health

Frankston, Victoria, Australia

NOT YET RECRUITING

NEXT Oncology

Barcelona, Barcelona, Spain

RECRUITING

Vall d'Hebron Institute of Oncology

Barcelona, Barcelona, Spain

RECRUITING

NEXT Oncology

Madrid, Spain

RECRUITING

Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; apalutamide; darolutamide; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Pratik S. Multani, MD

  ORIC Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

ORIC Clinical

CONTACT

650-388-5600; clinical@oricpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interval 3+3 dose escalation design

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 10, 2022
• Study Start: June 1, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

AU (3); GB (1); US (20); ES (3)