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Testing ORIC-944 for metastatic prostate cancer treatment

An Open-Label, Phase 1/1b Study of ORIC-944 as a Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer

Phase 1 Interventional ORIC Pharmaceuticals · NCT05413421

This study is testing a new drug called ORIC-944 to see if it can safely help people with metastatic prostate cancer, both on its own and when combined with other treatments.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment250 (estimated)
Ages18 Years and up
SexMale
SponsorORIC Pharmaceuticals Industry-sponsored
Drugs / interventionschemotherapy
Locations27 sites (Colorado Springs, Colorado and 26 other locations)
Trial IDNCT05413421 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and preliminary effectiveness of ORIC-944, a selective small molecule inhibitor targeting PRC2, in patients with metastatic prostate cancer. The study is divided into three parts: the first part assesses ORIC-944 as a standalone treatment, the second part examines its use in combination with various Androgen Receptor Pathway Inhibitors (ARPIs), and the third part focuses on optimizing the dosage of ORIC-944 in combination with ARPIs. The trial is designed to identify the maximum tolerated dose and gather initial data on its antitumor activity.

Who should consider this trial

Good fit: Ideal candidates include men with metastatic prostate cancer who have progressed after prior ARPI treatments.

Not a fit: Patients who have not received any prior ARPI treatment or those with non-metastatic prostate cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with metastatic prostate cancer who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in its specific application, similar studies targeting PRC2 dysregulation have shown promise in other cancer types.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Colorado Springs, Colorado and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Prostate CancerPRC2 dysregulationEEDCRPCmCRPCARPI
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.