Study of ORIC-944 in Patients With Metastatic Prostate Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ORIC-944, Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets, Apalutamide (Erleada™) 60 mg or 240 mg tablets, Darolutamide (Nubeqa®) 300 mg tablets.
- Who it may be relevant to
- Registry conditions: Metastatic Prostate Cancer. Basic parameters: from 18 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Spain, United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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.
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.
Interventions
- 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
Primary outcome measures
- Recommended Phase 2 Dose (RP2D) [Time frame: 12 months]
- Maximum plasma concentration (Cmax) [Time frame: 28 Days]
- Time to maximum observed concentration (Tmax) [Time frame: 28 Days]
- Area under the curve (AUC) [Time frame: 28 Days]
- Apparent plasma terminal elimination half-life (t1/2) [Time frame: 28 Days]
Secondary outcome measures (5)
- Clinical benefit rate (CBR) [Time frame: 36 months]
- Objective response rate (ORR) [Time frame: 36 months]
- Duration of response (DOR) [Time frame: 36 months]
- Progression-free survival (PFS) [Time frame: 36 months]
- On-treatment PSA levels and change from baseline [Time frame: 36 months]
Eligibility 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 20 centers
- Rocky Mountain Cancer Center — Colorado Springs
- South Florida Oncology and Hematology — Plantation
- Illinois Cancer Specialists — Arlington Heights
- Comprehensive Urologic Care — Lake Barrington
- First Urology — Jeffersonville
- Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland — Baltimore
- Maryland Oncology Hematology — Silver Spring
- Karmanos — Detroit
- … and 12 more centers
Australia · 3 centers
- Sydney Adventist Health — Wahroonga
- Bendigo Health — Bendigo
- Peninsula Health — Frankston
Spain · 3 centers
- NEXT Oncology — Barcelona
- Vall d'Hebron Institute of Oncology — Barcelona
- NEXT Oncology — Madrid
United Kingdom · 1 center
- Royal Marsden NHS Foundation Trust — Sutton
Identifiers
NCT: NCT05413421 · ORIC-944-01