Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

Официальное название

An Open-Label, Phase 1/2 Study of ORIC-114 as a Single Agent or in Combination With Chemotherapy, in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

Обзор

The purpose of this study is to establish the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of ORIC-114 as a Single Agent or in Combination with Chemotherapy when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.

Подробное описание

ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR and HER2 alterations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.

This is a first-in-human, open-label, single arm, multicenter, dose escalation study of ORIC-114 as a single agent (Part I), followed by dose optimization (Part II) to establish the recommended phase 2 dose (RP2D) and antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options. After the optimal RP2D has been determined, Phase 2 will be initiated via protocol amendment to add one or more expansion cohorts of patients with specific tumor types, treatment history, and/or expression of a specific biomarker to evaluate the antitumor activity of ORIC-114.

After completion of Part I dose escalation, Part III, a dose escalation study of ORIC-114 in combination with chemotherapy (carboplatin-pemetrexed) may be initiated to establish the RP2D and/or MTD and antitumor activity for the combination (US sites only).

Вмешательства

• Препарат ORIC-114
  ORIC-114 oral daily
• Препарат Chemotherapy drug
  21 days for up to 4 cycles

Первичные конечные точки

• Recommended Phase 2 Dose (RP2D) [Срок оценки: 12 months]
• Maximum plasma concentration (Cmax) [Срок оценки: 28 Days]
• Time of 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 (6)

• Objective response rate (ORR) [Срок оценки: 36 months]
• Duration of response (DOR) [Срок оценки: 36 months]
• Clinical benefit rate (CBR) [Срок оценки: 36 months]
• Progression-free survival (PFS) [Срок оценки: 36 months]
• Intracranial response rate (CR and/or PR) [Срок оценки: 36 months]
• Intracranial progression-free survival (PFS) [Срок оценки: 36 months]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation or atypical EGFR mutation as determined by any nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test

• Part I Dose Escalation (CLOSED) Any solid tumor with

• EGFR exon 20 insertion mutation
• HER2 exon 20 insertion mutation
• Atypical EGFR mutations (NSCLC only) (Appendix 8)
• HER2 amplification or overexpression (HER2+)
• Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
• Part I Extension (ONGOING)

• Cohort IA: Patients with HER2+ breast cancer previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
• Cohort IB: NSCLC patients with EGFR exon 20 insertion mutation previously treated with chemotherapy and amivantamab
• Cohort IC: Treatment-naïve NSCLC patients with EGFR exon 20 insertion mutation
• Cohort ID: Treatment-naïve NSCLC patients with EGFR atypical mutations
• Part II Dose Optimization (ONGOING): NSCLC patients with

• Cohort IIA: EGFR exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to an EGFR exon 20 targeted agent, ie, must have declined or be ineligible for all available exon 20 targeted therapies with proven benefit
• Cohort IIB: HER2 exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to a HER2 exon 20 targeted TKI
• Cohort IIC: Atypical EGFR mutation, patients may have received a prior EGFR TKI
• Agreement and ability to undergo pretreatment biopsy
• Measurable disease according to RECIST 1.1
• CNS involvement, which is either previously treated and controlled, or untreated and asymptomatic
• ECOG performance status of 0 or 1
• Adequate organ function

Критерии исключения

• Known EGFR T790M mutation
• Leptomeningeal disease and spinal cord compression

\-- Except if LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator; the subject must be free of neurological symptoms of LMD

• 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
• Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
• Known, symptomatic human immunodeficiency virus (HIV) infection
• Known active infection requiring treatment or history of hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients positive for HBsAg but normal HBV DNA level are allowed.
• Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes
• Any other concurrent serious uncontrolled medical, psychological, or addictive conditions

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 · 17 центров

• City of Hope — Duarte
• City of Hope — Huntington Beach
• City of Hope — Irvine
• City of Hope — Long Beach
• University of California, San Francisco — San Francisco
• Yale Cancer Center — New Haven
• Georgetown University — Washington D.C.
• Mayo Clinic — Jacksonville
• … и ещё 9 центров

South Korea · 8 центров

• Chungbuk University Hospital — Cheongju-si
• National Cancer Center — Goyang-si
• Catholic University of Korea, St, Vincent Hospital — Gyeonggi-do
• Gachon University Hospital — Incheon
• Seoul National Bundang Hospital — Seongnam-si
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul
• Severance Hospital, Yonsei University Health System — Seoul

Малайзия · 5 центров

• Sultan Ahmad Shah Medical Centre at International Islamic University Malaysia (IIUM) — Kuantan
• Pulau Pinang Hospital — George Town
• Sarawak General Hospital (SGH) — Kuching
• Hospital Kuala Lumpur — Kuala Lumpur
• University of Malaya Medical Center (UMMC) — Kuala Lumpur

Австралия · 4 центра

• Chris O'Brien Lifehouse — Camperdown
• Peter MacCallum Cancer Centre — Melbourne
• One Clinical Research, Hollywood Medical Centre — Nedlands
• Sydney Adventist Health — Sydney

Испания · 3 центра

• NEXT Oncology - Barcelona — Barcelona
• Vall d'Hebron Institute of Oncology (VHIO) — Barcelona
• NEXT Oncology - Madrid — Madrid

Канада · 1 центр

• Princess Margaret Cancer Centre — Toronto

Гонконг · 1 центр

• The Chinese University of Hong Kong — Shatin

Польша · 1 центр

• Medical University of Gdańsk — Gdansk

Тайвань · 1 центр

• National Taiwan University Hospital — Taipei

Великобритания · 1 центр

• The Christie NHS Foundation Trust — Manchester

Идентификаторы

NCT: NCT05315700 · ORIC-114-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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