A Phase 1 Multiple Expansion Cohort Trial of MRTX1719 in Patients With Advanced Solid Tumors With Homozygous MTAP Deletion
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 336
- 试验地点
- 46
- 主要终点
- Number of Patients who Experience Dose-Limiting Toxicity
研究概览
简要总结
This is a Phase 1, open-label, multicenter, study of the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.
详细描述
This first-in-human clinical trial will begin with an exploration of MRTX1719 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure sufficient safety experience, PK information, compare food effect and relative bioavailability between capsules and tablets, and early evidence of clinical activity are available.
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 with homozygous deletion of the MTAP gene detected in tumor tissue.
- •Unresectable or metastatic disease.
- •Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function.
排除标准
- •Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
- •Active brain metastases or carcinomatous meningitis.
- •History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
- •Major surgery within 4 weeks of first dose of study treatment.
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
- •Cardiac abnormalities.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Phase 1b Sub-study 5
干预措施: MRTX1719 (Drug)
Phase 1/1B
Dose Escalation/Evaluation
干预措施: MRTX1719 (Drug)
Phase 1b Sub-studies 1-4
干预措施: MRTX1719 (Drug)
结局指标
主要结局
Number of Patients who Experience Dose-Limiting Toxicity
时间窗: 21 days
Number of patients who experience a treatment-related adverse event
时间窗: Up to 2 years
Objective response rate (ORR)
时间窗: 2 years
Duration of response (DOR)
时间窗: 2 years
Duration of response (DOR)
时间窗: 2 years
Progression free survival (PFS)
时间窗: 2 years
Overall survival (OS)
时间窗: 2 years
Number of Patients With Clinically Significant Laboratory Assessments
时间窗: Up to 4 years
Number of Patients who Experience Dose-Limiting Toxicity
时间窗: 21 days
Number of patients who experience a treatment-related adverse event
时间窗: Up to 2 years
Objective response rate (ORR)
时间窗: 2 years
次要结局
- Time to achieve maximal plasma concentration (Tmax)(Up to 4 days)
- Terminal elimination half-life (t1/2)(Up to 4 days)
- Area under the plasma concentration versus time curve (AUC)(Up to 4 days)
- Maximum observed plasma concentration (Cmax)(Up to 4 days)
- Apparent total plasma clearance when dosed orally (CL/F)(Up to 4 days)
- Apparent volume of distribution when dosed orally (Vz/F)(Up to 4 days)