A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 63
- 试验地点
- 14
- 主要终点
- Phase 1/1b: Number of patients who experience a treatment-related adverse event
研究概览
简要总结
A Phase 1/2 study of MRTX1133 in solid tumors harboring a KRAS G12D mutation.
详细描述
This first-in-human clinical trial will begin with an exploration of MRTX1133 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure collection of sufficient safety and PK information, and early evidence of clinical activity are available to recommend Phase 2 regimens. In Phase 2, separate cohorts of patients by histological diagnosis and/or baseline characteristics will be evaluated for the clinical activity and efficacy of MRTX1133.
This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.
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
- •Histologically confirmed diagnosis of a solid tumor malignancy harboring KRAS G12D mutation in tumor tissue or ctDNA.
- •Unresectable or metastatic disease.
- •Patients must have received standard therapies appropriate for their tumor type and stage; first-line treatment for PDAC for certain cohorts.
- •Presence of tumor lesions to be evaluated per RECIST v1.1:
- •in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease.
- •in the Phase 1b and Phase 2 cohorts, patients must have measurable disease.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function.
- •Age ≥ 18 years
排除标准
- •Active brain metastases or carcinomatous meningitis.
- •Prior treatment with a KRAS G12D inhibitor (Phase 1b & Phase 2 only).
- •History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow oral medications.
- •History of malignant small bowel obstruction.
- •Cardiac abnormalities.
研究组 & 干预措施
Phase 1/1B
Dose Escalation/Evaluation
干预措施: MRTX1133 (Drug)
Phase 2
MRTX1133 recommended Phase 2 dose administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12D mutation to include the following: NSCLC, PDAC, CRC, Other Solid Tumors
干预措施: MRTX1133 (Drug)
结局指标
主要结局
Phase 1/1b: Number of patients who experience a treatment-related adverse event
时间窗: Up to 2 years
Phase 2: Objective response rate (ORR)
时间窗: 2 years
Phase 2: Progression free survival (PFS)
时间窗: 2 years
Phase 1: Number of Patients who Experience Dose-Limiting Toxicity
时间窗: 21 Days
Phase 2: Duration of response (DOR)
时间窗: 2 years
Phase 2: Overall survival (OS)
时间窗: 2 years
次要结局
- Apparent total plasma clearance when dosed orally (CL/F)(up to 4 days)
- Maximum observed plasma concentration (Cmax)(up to 4 days)
- Area under plasma concentration versus time curve (AUC)(up to 4 days)
- Terminal elimination half-life (t1/2)(up to 4 days)
- Apparent volume of distribution when dosed orally (Vz/F)(up to 4 days)
- Time to achieve maximal plasma concentration (Tmax)(up to 4 days)