Study of ORIC-944 in Patients With Metastatic Prostate Cancer

Metastatic Prostate Cancer Clinical Trial

Official title:

An Open-Label, Phase 1/1b, Study of ORIC-944 in Patients With Metastatic Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05413421
• Other study ID #: ORIC-944-01
• Status: Recruiting
• Phase: Phase 1
• Start date: June 1, 2022
• Est. completion date: June 2024

Study information

• Verified date: April 2023
• Source: ORIC Pharmaceuticals
• Contact: ORIC Clinical
• Phone: 650-388-5600
• Email: clinical[@]oricpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: June 2024
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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
• 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

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Neuroendocrine Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ORIC-944
ORIC-944 oral once daily for 28 days

Locations

Country	Name	City	State
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Urology Clinics of North Texas	Dallas	Texas
United States	Karmanos	Detroit	Michigan
United States	Keystone Urology Specialists	Lancaster	Pennsylvania
United States	Memorial Sloane Kettering Cancer Center	New York	New York
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
ORIC Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase 2 Dose (RP2D)	RP2D as determined by interval 3+3 dose escalation design	12 months
Primary	Maximum plasma concentration (Cmax)	PK of ORIC-944	28 Days
Primary	Time to maximum observed concentration (Tmax)	PK of ORIC-944	28 Days
Primary	Area under the curve (AUC)	PK of ORIC-944	28 Days
Primary	Apparent plasma terminal elimination half-life (t1/2)	PK of ORIC-944	28 Days
Secondary	Clinical benefit rate (CBR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Objective response rate (ORR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Duration of response (DOR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Progression-free survival (PFS)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months