Now Enrolling: ORIC-944-01: 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

ORIC-944 is an investigational agent and not approved by the US Food and Drug Administration (FDA) or any other regulatory agency in any country.

Mechanism of Action: ORIC-944 is a potent, highly selective, allosteric, orally bioavailable, small molecule inhibitor of PRC2 via binding the EED subunit. 

About the Study: This is a first-in-human, open-label, multicenter, dose escalation study of ORIC-944 as a single agent (Part I - COMPLETED) or in combination with an Androgen Receptor Pathway Inhibitor (ARPI) (apalutamide or darolutamide) (Part II) to establish the safety and preliminary antitumor activity of ORIC-944 as a single agent and in combination with the ARPIs in patients with metastatic prostate cancer. Part III (dose optimization) of the protocol will explore 2 potential dose levels of ORIC-944 selected from Part II in combinations with ARPIs to select the final RP2D for each combination across two separate patient populations.

In Part II, escalating dose levels of ORIC-944 will be administered orally, QD in 28-day cycles in combinations with apalutamide 240 mg QD or darolutamide 600 mg BID. Combinations with abiraterone and enzalutamide may be initiated in the future.

In Part III dose optimization, patients will be randomized 1:1 across two doses of ORIC-944 selected from Part II in combination initially with apalutamide or darolutamide, in each of two separate patient populations as shown in the study schema below.

Who may qualify for the study:

• Patients with metastatic prostate cancer, maintaining castrate levels of testosterone and who are ≥18 years
• Must have received only 1 prior line of ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) in any setting; may also have received up to 1 prior line of chemotherapy in mCSPC 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 ie, presence of bone lesions on a bone scan and/or at least one measurable lesion per RECIST 1.1
  • Agreement and ability to undergo on-study punch skin biopsies
  • ECOG performance status 0 - 1
  • Adequate organ function

 
Who are excluded from the study:

• 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

*This is not a complete list of criteria for participation and other study requirements may apply

If you are a physician or health care provider interested in prostate cancer treatment, you can find more information about the trial at https://clinicaltrials.gov/study/NCT05315700?term=ORIC-114&rank=2.

Additional Information:

• The ARPIs will be provided to the patients free of cost
• Patients may receive reimbursement for approved travel expenses associated with visits for the study assessments

Study Contact Information:

Central Contact Person: ORIC Clinical

Telephone: 650-388-5600

Email: [email protected]