A Phase 1 interventional study of ORIC-944 and Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets in Metastatic Prostate Cancer, sponsored by ORIC Pharmaceuticals. Recruiting at 27 sites in 4 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by ORIC Pharmaceuticals · Phase 1, Interventional, and Treatment
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.
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.
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 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
Exclusion Criteria:
ORIC-944 dosed orally on a continuous daily dosing regimen in 28-day cycles
Drug: ORIC-944
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 · 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
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 · Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets · Drug: Darolutamide (Nubeqa®) 300 mg tablets
Oral, once daily, continuous
Oral, 1000 mg once daily, continuous
Oral, 240 mg once daily, continuous
Oral, 600 mg twice daily, continuous
Oral, 160 mg once daily, continuous
Recommended Phase 2 Dose (RP2D)
RP2D as determined by interval 3+3 dose escalation design
Time frame: 12 months
Maximum plasma concentration (Cmax)
PK of ORIC-944 single agent and in combination with an ARPI
Time frame: 28 Days
Time to maximum observed concentration (Tmax)
PK of ORIC-944 single agent and in combination with an ARPI
Time frame: 28 Days
Area under the curve (AUC)
PK of ORIC-944 single agent and in combination with an ARPI
Time frame: 28 Days
Apparent plasma terminal elimination half-life (t1/2)
PK of ORIC-944 single agent and in combination with an ARPI
Time frame: 28 Days
Clinical benefit rate (CBR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 36 months
Objective response rate (ORR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 36 months
Duration of response (DOR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 36 months
Progression-free survival (PFS)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 36 months
On-treatment PSA levels and change from baseline
Prostate cancer working group 3 criteria (PCWG3)
Time frame: 36 months
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ORIC Pharmaceuticals