Metastatic Prostate CancerPhase 1NCT05413421
Study of ORIC-944 in Patients With Metastatic Prostate Cancer
A Phase 1 study testing ORIC-944, Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets and Apalutamide (Erleada™) 60 mg or 240 mg tablets in people with Metastatic Prostate Cancer, run by ORIC Pharmaceuticals at 27 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- ORIC-944, Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets and Apalutamide (Erleada™) 60 mg or 240 mg tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 275 participants
- Where
- 27 sitesin 4 countries
- Study dates
- 1 Jun 2022to Apr 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 16Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
27 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
27 sites in 4 countries
United States20 sites, 20 recruiting
- Recruiting
Amarillo Urology Research
Amarillo, Texas, 74035
- Recruiting
Illinois Cancer Specialists
Arlington Heights, Illinois, 60005
- Not yet recruiting
MidLantic Urology
Bala-Cynwyd, Pennsylvania, 19004
- Recruiting
Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
Baltimore, Maryland, 21201
- Recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
- Recruiting
Rocky Mountain Cancer Center
Colorado Springs, Colorado, 80907
- Recruiting
Urology Clinics of North Texas
Dallas, Texas, 75231
- Recruiting
Karmanos
Detroit, Michigan, 48201
- Recruiting
Virginia Oncology Associates
Fairfax, Virginia, 22031
- Recruiting
First Urology
Jeffersonville, Indiana, 47130
- Recruiting
Comprehensive Urologic Care
Lake Barrington, Illinois, 60010
- Recruiting
Keystone Urology Specialists
Lancaster, Pennsylvania, 17601
- Not yet recruiting
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
- Recruiting
Minnesota Oncology Hematology
Minneapolis, Minnesota, 55404
- Recruiting
Memorial Sloane Kettering Cancer Center
New York, New York, 10065
- Not yet recruiting
Virginia Cancer Specialists
Norfolk, Virginia, 23502
- Recruiting
South Florida Oncology and Hematology
Plantation, Florida, 33322
- Recruiting
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
- Recruiting
University of Washington, Fred Hutchinson Cancer Center
Seattle, Washington, 98109
- Recruiting
Maryland Oncology Hematology
Silver Spring, Maryland, 20904
Australia3 sites, 3 recruiting
- Recruiting
Bendigo Health
Bendigo, Victoria
- Not yet recruiting
Peninsula Health
Frankston, Victoria
- Recruiting
Sydney Adventist Health
Wahroonga, New South Wales
Spain3 sites, 3 recruiting
- Recruiting
NEXT Oncology
Barcelona, Barcelona
- Recruiting
Vall d'Hebron Institute of Oncology
Barcelona, Barcelona
- Recruiting
NEXT Oncology
Madrid
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Marsden NHS Foundation Trust
Sutton, Surrey
About this study
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
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.
Read the 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.
- Conditions
- Metastatic Prostate Cancer
- Being tested
- ORIC-944, Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets, Apalutamide (Erleada™) 60 mg or 240 mg tablets, Darolutamide (Nubeqa®) 300 mg tablets, Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets
- Keywords
- PRC2 dysregulation, EED, CRPC, mCRPC, ARPI
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORIC-944Drug
Oral, once daily, continuous
Abiraterone acetate (Zytiga®) 250 mg or 500 mg tabletsDrug
Oral, 1000 mg once daily, continuous
Apalutamide (Erleada™) 60 mg or 240 mg tabletsDrug
Oral, 240 mg once daily, continuous
Darolutamide (Nubeqa®) 300 mg tabletsDrug
Oral, 600 mg twice daily, continuous
Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tabletsDrug
Oral, 160 mg once daily, continuous
| Study group | Role | What they receive |
|---|---|---|
| Single Agent Dose Escalation | Experimental | ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles Receives: Drug: ORIC-944 |
| Combination Dose Escalation | Experimental | ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles in combinations with abiraterone, apalutamide, darolutamide, or enzalutamide Receives: Drug: ORIC-944; Drug: Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets; Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Darolutamide (Nubeqa®) 300 mg tablets; Drug: Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets |
| Combination Dose Optimization | Experimental | 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 Receives: Drug: ORIC-944; Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Darolutamide (Nubeqa®) 300 mg tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D)
RP2D as determined by interval 3+3 dose escalation design
Measured: 12 months
Maximum plasma concentration (Cmax)
PK of ORIC-944 single agent and in combination with an ARPI
Measured: 28 Days
Time to maximum observed concentration (Tmax)
PK of ORIC-944 single agent and in combination with an ARPI
Measured: 28 Days
Area under the curve (AUC)
PK of ORIC-944 single agent and in combination with an ARPI
Measured: 28 Days
Apparent plasma terminal elimination half-life (t1/2)
PK of ORIC-944 single agent and in combination with an ARPI
Measured: 28 Days
Secondary outcomes (5)
Clinical benefit rate (CBR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Objective response rate (ORR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Duration of response (DOR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Progression-free survival (PFS)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
On-treatment PSA levels and change from baseline
Prostate cancer working group 3 criteria (PCWG3)
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start1 Jun 2022
- Primary completionJun 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Interval 3+3 dose escalation design
- Masking
- None (open label)
- Enrolment
- 275 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ORIC Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pratik S. Multani, MD, Study director, ORIC Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05413421
- Sponsor's protocol ID
- ORIC-944-01
- Status last verified
- Jul 2026
- First submitted
- 7 Jun 2022
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No