Study of ORIC-944 in Patients With Metastatic Prostate Cancer

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат ORIC-944
  Oral, once daily, continuous
• Препарат Abiraterone acetate (Zytiga®) 250 mg or 500 mg tablets
  Oral, 1000 mg once daily, continuous
• Препарат Apalutamide (Erleada™) 60 mg or 240 mg tablets
  Oral, 240 mg once daily, continuous
• Препарат Darolutamide (Nubeqa®) 300 mg tablets
  Oral, 600 mg twice daily, continuous
• Препарат Enzalutamide (Xtandi®) 40 mg capsules or 40 mg and 80 mg tablets
  Oral, 160 mg once daily, continuous

Первичные конечные точки

• Recommended Phase 2 Dose (RP2D) [Срок оценки: 12 months]
• Maximum plasma concentration (Cmax) [Срок оценки: 28 Days]
• Time to maximum observed concentration (Tmax) [Срок оценки: 28 Days]
• Area under the curve (AUC) [Срок оценки: 28 Days]
• Apparent plasma terminal elimination half-life (t1/2) [Срок оценки: 28 Days]

Вторичные конечные точки (5)

• Clinical benefit rate (CBR) [Срок оценки: 36 months]
• Objective response rate (ORR) [Срок оценки: 36 months]
• Duration of response (DOR) [Срок оценки: 36 months]
• Progression-free survival (PFS) [Срок оценки: 36 months]
• On-treatment PSA levels and change from baseline [Срок оценки: 36 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 20 центров

• Rocky Mountain Cancer Center — Colorado Springs
• South Florida Oncology and Hematology — Plantation
• Illinois Cancer Specialists — Arlington Heights
• Comprehensive Urologic Care — Lake Barrington
• First Urology — Jeffersonville
• Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland — Baltimore
• Maryland Oncology Hematology — Silver Spring
• Karmanos — Detroit
• … и ещё 12 центров

Австралия · 3 центра

• Sydney Adventist Health — Wahroonga
• Bendigo Health — Bendigo
• Peninsula Health — Frankston

Испания · 3 центра

• NEXT Oncology — Barcelona
• Vall d'Hebron Institute of Oncology — Barcelona
• NEXT Oncology — Madrid

Великобритания · 1 центр

• Royal Marsden NHS Foundation Trust — Sutton

Идентификаторы

NCT: NCT05413421 · ORIC-944-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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