A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 36
- 主要终点
- Incidence of Adverse Events (Escalation Phase)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Expansion (Part 2, Module A)
Expansion Module A Part 2 inlexisertib combination closed on January 8, 2024, with no participants enrolled.
干预措施: Inlexisertib (Drug)
Expansion (Part 2, Module B)
Inlexisertib tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST).
干预措施: Ripretinib (Drug)
Dose Escalation (Part 1, Module A)
Escalation Module A Part 1 inlexisertib combination closed on January 8, 2024, with no participants enrolled.
干预措施: Inlexisertib (Drug)
Expansion (Part 2, Module B)
Inlexisertib tablets will be administered in combination with ripretinib in 28-day cycles to evaluate preliminary efficacy in participants with 2nd-line advanced gastrointestinal stromal tumor (GIST).
干预措施: Inlexisertib (Drug)
Dose Escalation (Part 1, Module B)
Inlexisertib tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).
干预措施: Ripretinib (Drug)
Dose Escalation (Part 1, Module B)
Inlexisertib tablets in escalating dose cohorts in 28-day cycles will be administered in combination with ripretinib once daily (QD).
干预措施: Inlexisertib (Drug)
结局指标
主要结局
Incidence of Adverse Events (Escalation Phase)
时间窗: Approximately 24 months
Identify the observed adverse events and serious adverse events associated with inlexisertib in combination with other anticancer therapies.
Recommended Phase 2 Doses (RP2D) (Escalation Phase)
时间窗: Approximately 18 months
Identify the dose-limiting toxicities for each dose level tested and determine the recommended Phase 2 doses of inlexisertib in combination with other anticancer therapies.
Objective response rate (ORR) (Expansion Phase)
时间窗: Approximately 24 months
Proportion of participants who achieve CR or PR per histology-specific consensus response criteria.
次要结局
- Overall Survival (OS)(Approximately 48 months)
- Maximum observed concentration (Cmax)(Predose and up to 12 hours postdose)
- Time to maximum observed concentration (Tmax)(Predose and up to 12 hours postdose)
- Minimum observed concentration (Cmin)(Predose and up to 12 hours postdose)
- Area under the concentration-time curve (AUC)(Predose and up to 12 hours postdose)
- Duration of response (DoR)(Approximately 24 months)
- Disease Control Rate (DCR)(Approximately 24 months)
- Time to response(Approximately 24 months)
- Progression-free survival (PFS)(Approximately 24 months)