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Study of ORIC-944 in Patients with Metastatic Prostate Cancer

PHASE1RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2022-06-01

Primary completion: 2024-12-01

Study completion finish: 2026-09-01

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT05413421

Intervention or treatment

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

Conditions

• Metastatic Prostate Cancer

Image related to Metastatic Prostate Cancer

Condition: Metastatic Prostate Cancer
DRUG: ORIC-944 and other drugs
Wahroonga, New South Wales, Australia and more
Sponsor: ORIC Pharmaceuticals

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Sydney Adventist Health

Research sites nearby

Select from list below to view details:

Sydney Adventist Health
Wahroonga, New South Wales, Australia
Bendigo Health
Bendigo, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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
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

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Recommended Phase 2 Dose (RP2D)	RP2D as determined by interval 3+3 dose escalation design	12 months
Maximum plasma concentration (Cmax)	PK of ORIC-944 single agent and in combination with an ARPI	28 Days
Time to maximum observed concentration (Tmax)	PK of ORIC-944 single agent and in combination with an ARPI	28 Days
Area under the curve (AUC)	PK of ORIC-944 single agent and in combination with an ARPI	28 Days
Apparent plasma terminal elimination half-life (t1/2)	PK of ORIC-944 single agent and in combination with an ARPI	28 Days

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Clinical benefit rate (CBR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Objective response rate (ORR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Duration of response (DOR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Progression-free survival (PFS)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
On-treatment PSA levels and change from baseline	Prostate cancer working group 3 criteria (PCWG3)	36 months

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

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References

Clinical Trials Gov: Study of ORIC-944 in Patients with Metastatic Prostate Cancer