A Phase 1a/1b Study of the Safety, Pharmacokinetics, and Antitumor Activity of the Oral Menin Inhibitor Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) After Imatinib Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 157
- 试验地点
- 53
- 主要终点
- Dose Escalation: Dose Limiting Toxicity (DLT)
研究概览
简要总结
In this clinical trial, the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib will be evaluated in adults with gastrointestinal stromal tumors (GIST) who have been treated previously with imatinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Documented diagnosis of advanced/metastatic KIT-mutant GIST.
- •Documented disease progression on imatinib as current or prior therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 at screening.
- •At least 1 measurable lesion per RECIST v1.1 modified for GIST.
- •Negative pregnancy test for participants of childbearing potential.
- •Adequate organ function per protocol requirements.
- •Resolution of all clinically significant toxicities from prior therapy to <Grade 1 (or participant baseline) within 1 week before the first dose of study intervention.
- •Participant, or legally authorized representative, must be able to understand and provide written informed consent before the first screening procedure.
排除标准
- •Diagnosis of GIST without a KIT mutation or with a T670X KIT mutation.
- •History of prior or current cancer that has potential to interfere with obtaining study results.
- •Received a prohibited medication, including investigational therapy, less than 14 days or within 5 drug half-lives before the first dose of study intervention.
- •Active central nervous system metastases.
- •Uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
- •Mean corrected QT interval (QTcF) greater than 470ms.
- •Left ventricular ejection fraction (LVEF) <50%.
- •Major surgery within 2 weeks before the first dose of study intervention.
- •Is pregnant or breastfeeding.
- •Gastrointestinal abnormalities that may impact taking study intervention by mouth.
- •Actively bleeding, excluding hemorrhoidal or gum bleeding.
研究组 & 干预措施
Dose Escalation
Ziftomenib plus imatinib
干预措施: ziftomenib (Drug)
Dose Escalation
Ziftomenib plus imatinib
干预措施: imatinib mesylate (Drug)
Recommended Phase 2 Dose Determination
Ziftomenib plus imatinib
干预措施: ziftomenib (Drug)
Recommended Phase 2 Dose Determination
Ziftomenib plus imatinib
干预措施: imatinib mesylate (Drug)
Dose Expansion
Ziftomenib plus imatinib
干预措施: ziftomenib (Drug)
Dose Expansion
Ziftomenib plus imatinib
干预措施: imatinib mesylate (Drug)
结局指标
主要结局
Dose Escalation: Dose Limiting Toxicity (DLT)
时间窗: Cycle 1 (first 28 day cycle)
Rate of DLTs per dose level
Descriptive statistics of Adverse Events (AEs)
时间窗: First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the participant is lost to follow-up, whichever comes first
Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Dose Expansion: Clinical benefit rate (CBR)
时间窗: Up to 2 years following start of treatment with ziftomenib
CBR is the rate of participants achieving complete response (CR), partial response (PR), or stable disease (SD), assessed per Response Criteria in Solid Tumors (RECIST) v1.1 modified for GIST
次要结局
- Recommended Phase 2 Dose Determination and Dose Expansion: CBR(Up to 2 years following start of treatment with ziftomenib)
- Overall Response Rate (ORR)(Up to 2 years following start of treatment with ziftomenib)
- Progression Free Survival (PFS)(Up to 2 years following start of treatment with ziftomenib)
- Duration of Response (DoR)(Up to 2 years following start of treatment with ziftomenib)
- Overall Survival (OS)(Up to 2 years following start of treatment with ziftomenib)
- Maximum plasma concentration (Cmax)(Day 1 of each cycle; each cycle is 28 days)
- Time to maximum plasma concentration (Tmax)(Day 1 of each cycle; each cycle is 28 days)
- Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last)(Day 1 of each cycle; each cycle is 28 days)
- Area under the concentration-time curve over a dosing interval (AUC tau)(Day 1 of each cycle; each cycle is 28 days)