A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced Malignancies

Официальное название

A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies

Обзор

This is a Phase 1/2, multicenter, open-label (unless otherwise specified in a combination-specific module) study of inlexisertib in combination with anticancer therapies. Modules within the master protocol are defined according to different combinations of inlexisertib with other anticancer agents.

Вмешательства

• Препарат Inlexisertib
  Oral Tablet Formulation
• Препарат Ripretinib
  Oral Tablet Formulation

Первичные конечные точки

• Incidence of Adverse Events (Escalation Phase) [Срок оценки: Approximately 24 months]
• Recommended Phase 2 Doses (RP2D) (Escalation Phase) [Срок оценки: Approximately 18 months]
• Objective response rate (ORR) (Expansion Phase) [Срок оценки: Approximately 24 months]

Вторичные конечные точки (9)

• Duration of response (DoR) [Срок оценки: Approximately 24 months]
• Disease Control Rate (DCR) [Срок оценки: Approximately 24 months]
• Time to response [Срок оценки: Approximately 24 months]
• Progression-free survival (PFS) [Срок оценки: Approximately 24 months]
• Overall Survival (OS) [Срок оценки: Approximately 48 months]
• Maximum observed concentration (Cmax) [Срок оценки: Predose and up to 12 hours postdose]
• Time to maximum observed concentration (Tmax) [Срок оценки: Predose and up to 12 hours postdose]
• Minimum observed concentration (Cmin) [Срок оценки: Predose and up to 12 hours postdose]
• Area under the concentration-time curve (AUC) [Срок оценки: Predose and up to 12 hours postdose]

Критерии участия

Критерии включения

• Male or female ≥18 years of age
• Module A: Part 1 and Part 2:

Module A Part 1 and Part 2 inlexisertib combination closed on January 8, 2024, with no participants enrolled.

• Module B: Only for Part 1 (Safety/Dose-finding):

• Pathologically confirmed diagnosis of GIST with a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation
• Must have progressed on at least one approved systemic regimen given in the locally advanced or metastatic setting or have documented intolerance to it
• Must not have received prior ripretinib treatment
• Module B: Only for Part 2 (Expansion)

• Pathologically confirmed GIST with documented mutation in KIT exon 11
• Must have progressed on imatinib given in the locally advanced or metastatic setting or have been intolerant to imatinib and may not have received additional systemic therapy for GIST
• Must have at least 1 measurable lesion according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
• Must have a life expectancy of more than 3 months and an ECOG performance status of 0-1
• Adequate organ function and bone marrow reserve based on laboratory assessments performed at Screening
• Must provide a fresh tumor biopsy, if able

Критерии исключения

• Must not have received the following within the specified time periods prior to the first dose of study drug:

• Medications, including anticancer therapies, that are known strong or moderate inhibitors or inducers of CYP3A4 or P-glycoprotein (P-gp) including certain herbal medications (eg, St. John's wort): 14 days or 5×the half-life of the medication (whichever is longer)
• Other anticancer therapies and any investigational therapies with a known safety and PK profile: 14 days or 5×the half-life of the medication (whichever is shorter)
• Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug-drug interactions and late toxicities of prior therapy as low, the Sponsor's Medical Monitor may approve a shorter washout of 14 days
• Grapefruit or grapefruit juice: 14 days
• Have not recovered from all clinically relevant toxicities from prior therapy
• New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug
• Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal disease
• Malabsorption syndrome
• Radiation for indications other than bone disease must have been completed 4 weeks prior to first dose of study drug, unless it consisted of limited field palliative radiation, including whole brain radiation, which must have been completed at least 2 weeks prior to first dose of study drug
• Major surgery within 4 weeks of the first dose of study drug
• Active HIV, Hepatitis B or Hepatitis C infection

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 · 11 центров

• University of Southern California - Norris Comprehensive Cancer Center — Los Angeles
• UCLA Department of Medicine-Hematology/Oncology — Los Angeles
• Sylvester Comprehensive Cancer Center — Miami
• University of Massachusetts Worcester — Worcester
• START Midwest — Grand Rapids
• Washington University School of Medicine - Siteman Cancer Center — St Louis
• Memorial Sloan Kettering Cancer Center - Main Campus — New York
• Cleveland Clinic Taussig Cancer Center — Cleveland
• … и ещё 3 центра

Испания · 4 центра

• ICO Hospitalet — Barcelona
• Hospital Universitario Ramón y Cajal — Madrid
• Hospital Universitario Clinico San Carlos — Madrid
• Hospital Universitario Virgen Del Rocio — Seville

Франция · 3 центра

• Centre Oscar Lambret — Lille
• Institut Curie, Service d'Oncologie Médicale — Paris
• Hôpital Européen Georges Pompidou — Paris

Италия · 3 центра

• AOU Careggi - Padiglione 16 - Piano Terra - Ambulatori Oncologici - Ufficio Trial — Florence
• IRCCS Azienda Ospedaliera Metropolitana — Genova
• Istituto Europeo di Oncologia — Milan

Германия · 2 центра

• Universitatsklinikum Franfurt — Frankfurt
• Universitätsklinikum Eppendorf — Hamburg

Нидерланды · 2 центра

• Antonie Van Leeuwenhoek Hospital — Amsterdam
• Radboudumc — Nijmegen

Дания · 1 центр

• Aarhus University Hospital — Aarhus

Португалия · 1 центр

• Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. — Porto

Швейцария · 1 центр

• Inselspital Universitätsklinikum Bern — Bern

Идентификаторы

NCT: NCT05957367 · DCC-3116-01-002 · 2024-516476-15-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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