An International, Phase 3, Randomized, Multicenter, Open-label Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With KIT Exon 11 and Co-occurring KIT Exons 17 and/or 18 Mutations Who Were Previously Treated With Imatinib
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 70
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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.
- •Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
- •Participants must have advanced GIST and radiologic progression on imatinib treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening.
- •Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
- •Participants of reproductive potential must agree to follow contraception requirements.
- •Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
- •Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.
排除标准
- •History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
- •Has known active central nervous system metastases.
- •New York Heart Association Class II-IV heart disease, myocardial infarction within 6 months of Cycle 1 Day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or congestive heart failure.
- •Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
- •Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
- •Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, acute or chronic hepatitis B, or acute or chronic hepatitis C infection.
- •Gastrointestinal abnormalities including, but not limited to:
- •inability to take oral medication
- •malabsorption syndromes
- •requirement for intravenous alimentation
- •Any active bleeding excluding hemorrhoidal or gum bleeding.
研究组 & 干预措施
Ripretinib
150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.
干预措施: Ripretinib (Drug)
Sunitinib
50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to end of treatment; up to approximately 48 months
The time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.
次要结局
- Objective Response Rate (ORR)(Up to end of treatment; up to approximately 48 months)
- Overall Survival (OS)(Up to approximately 48 months)