Study of ORIC-944 in Patients With Metastatic Prostate Cancer

Oric Pharmaceuticals

Status and phase

Enrolling

Phase 1

Conditions

Neuroendocrine Prostate Cancer

Metastatic Prostate Cancer

Treatments

Drug: ORIC-944

Study type

Interventional

Funder types

Industry

Identifiers

NCT05413421

ORIC-944-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 estimated patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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