Dysautonomia International

Study of ORIC-944 in Patients With Metastatic Prostate Cancer

Purpose

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.

Condition

Metastatic Prostate Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: Male
Accepts Healthy Volunteers: No

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

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Interval 3+3 dose escalation design
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Single Agent Dose Escalation	ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles	Drug: ORIC-944 Oral, once daily, continuous
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	Drug: ORIC-944 Oral, once daily, continuous Drug: Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets Oral, 1000 mg once daily, continuous Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets Oral, 240 mg once daily, continuous Drug: Darolutamide (Nubeqa®) 300 mg tablets Oral, 600 mg twice daily, continuous Drug: Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets Oral, 160 mg once daily, continuous
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	Drug: ORIC-944 Oral, once daily, continuous Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets Oral, 240 mg once daily, continuous Drug: Darolutamide (Nubeqa®) 300 mg tablets Oral, 600 mg twice daily, continuous

Recruiting Locations

Rocky Mountain Cancer Center
Colorado Springs, Colorado 80907

South Florida Oncology and Hematology
Plantation, Florida 33322

Illinois Cancer Specialists
Arlington Heights, Illinois 60005

Comprehensive Urologic Care
Lake Barrington, Illinois 60010

First Urology
Jeffersonville, Indiana 47130

Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
Baltimore, Maryland 21201

Maryland Oncology Hematology
Silver Spring, Maryland 20904

Karmanos
Detroit, Michigan 48201

Minnesota Oncology Hematology
Minneapolis, Minnesota 55404

Memorial Sloane Kettering Cancer Center
New York, New York 10065

Levine Cancer Institute
Charlotte, North Carolina 28204

Keystone Urology Specialists
Lancaster, Pennsylvania 17601

Amarillo Urology Research
Amarillo, Texas 74035

Urology Clinics of North Texas
Dallas, Texas 75231

Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah 84112

Virginia Oncology Associates
Fairfax, Virginia 22031

University of Washington, Fred Hutchinson Cancer Center
Seattle, Washington 98109

More Details

Status: Recruiting
Sponsor: ORIC Pharmaceuticals

Study Contact

ORIC Clinical
650-388-5600
clinical@oricpharma.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.