Study of ORIC-944 in Patients With Metastatic Prostate Cancer
- Conditions
- Metastatic Prostate Cancer
- Interventions
- Registration Number
- NCT05413421
- Lead Sponsor
- ORIC Pharmaceuticals
- Brief Summary
The purpose of this study is to establish recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) and preliminary antitumor activity of ORIC-944 in patients with metastatic prostate cancer.
- 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, single arm, multicenter, dose escalation followed by dose expansion study to establish the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) and preliminary antitumor activity of ORIC-944 in patients with metastatic prostate cancer, including those with neuroendocrine and/or small cell features, who have exhausted available treatment options.
The study will begin with dose finding in patients with metastatic prostate cancer (Dose Escalation); additional dose expansion cohorts (Dose Expansion), with specific histology, treatment history, and/or expression of a specific biomarker, may be initiated via protocol amendment The study will evaluate escalating dose levels of ORIC-944 administered orally, once daily in 28-day cycles following an interval 3+3 design.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 42
-
Patients with metastatic prostate cancer, including those with neuroendocrine prostate cancer (NEPC) and/or small cell features
-
Must have undergone bilateral orchiectomy or be willing to continue GnRH analogue or antagonist to maintain castrate levels of testosterone
-
Any number of prior therapies are allowed, but must have progressed after at least one line of next generation androgen receptor antagonist (abiraterone, enzalutamide, apalutamide, darolutamide) and must not have received more than 2 chemotherapy regimens in the mCRPC 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
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Measurable and/or evaluable disease by RECIST 1.1
-
Agreement and ability to undergo on-study punch skin biopsies and core tumor biopsies
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ECOG performance status of 0 or 1
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Adequate organ function
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination Dose Escalation Apalutamide (Erleada™) 60 mg or 240 mg tablets ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Combination Dose Optimization Apalutamide (Erleada™) 60 mg or 240 mg tablets 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 Combination Dose Escalation Darolutamide (Nubeqa®) 300 mg tablets ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Combination Dose Escalation Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Single Agent Dose Escalation ORIC-944 ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles Combination Dose Escalation ORIC-944 ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Combination Dose Escalation Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Combination Dose Optimization ORIC-944 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 Combination Dose Optimization Darolutamide (Nubeqa®) 300 mg tablets 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
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (RP2D) 12 months RP2D as determined by interval 3+3 dose escalation design
Maximum plasma concentration (Cmax) 28 Days PK of ORIC-944 single agent and in combination with an ARPI
Time to maximum observed concentration (Tmax) 28 Days PK of ORIC-944 single agent and in combination with an ARPI
Area under the curve (AUC) 28 Days PK of ORIC-944 single agent and in combination with an ARPI
Apparent plasma terminal elimination half-life (t1/2) 28 Days PK of ORIC-944 single agent and in combination with an ARPI
- Secondary Outcome Measures
Name Time Method Clinical benefit rate (CBR) 36 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Objective response rate (ORR) 36 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Duration of response (DOR) 36 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Progression-free survival (PFS) 36 months Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
On-treatment PSA levels and change from baseline 36 months Prostate cancer working group 3 criteria (PCWG3)
Trial Locations
- Locations (15)
South Florida Oncology and Hematology
🇺🇸Plantation, Florida, United States
First Urology
🇺🇸Jeffersonville, Indiana, United States
University of Washington, Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
🇺🇸Baltimore, Maryland, United States
Karmanos
🇺🇸Detroit, Michigan, United States
Memorial Sloane Kettering Cancer Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Keystone Urology Specialists
🇺🇸Lancaster, Pennsylvania, United States
Urology Clinics of North Texas
🇺🇸Dallas, Texas, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Sydney Adventist Health
🇦🇺Wahroonga, New South Wales, Australia
Bendigo Health
🇦🇺Bendigo, Victoria, Australia
NEXT Oncology
🇪🇸Madrid, Spain
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom