Clinical trial NCT05413421: Study of ORIC-944 in Patients with Metastatic Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Prostate Cancer
Keywords: PRC2 dysregulation
EED
CRPC
mCRPC
ARPI
Lead sponsor: ORIC Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-06-10
Enrollment: 250
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Interval 3+3 dose escalation design
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: 12 months
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 Days
measure: Time to maximum observed concentration (Tmax)
timeFrame: 28 Days
measure: Area under the curve (AUC)
timeFrame: 28 Days
measure: Apparent plasma terminal elimination half-life (t1/2)
timeFrame: 28 Days
Secondary outcomes:
measure: Clinical benefit rate (CBR)
timeFrame: 36 months
measure: Objective response rate (ORR)
timeFrame: 36 months
measure: Duration of response (DOR)
timeFrame: 36 months
measure: Progression-free survival (PFS)
timeFrame: 36 months
measure: On-treatment PSA levels and change from baseline
timeFrame: 36 months
Other outcomes:
Locations:
city: Plantation
country: United States
facility: South Florida Oncology and Hematology
state: Florida
city: Jeffersonville
country: United States
facility: First Urology
state: Indiana
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Karmanos
state: Michigan
city: New York
country: United States
facility: Memorial Sloane Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Lancaster
country: United States
facility: Keystone Urology Specialists
state: Pennsylvania
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington, Fred Hutchinson Cancer Center
state: Washington
city: Wahroonga
country: Australia
facility: Sydney Adventist Health
state: New South Wales
city: Bendigo
country: Australia
facility: Bendigo Health
state: Victoria
city: Barcelona
country: Spain
facility: NEXT Oncology
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Madrid
country: Spain
facility: NEXT Oncology
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
state: Surrey
Study officials:
affiliation: ORIC Pharmaceuticals
name: Pratik S. Multani, MD
role: STUDY_DIRECTOR
References: