A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 17
- 主要终点
- Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
研究概览
简要总结
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.
详细描述
This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.
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 with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
- •Unresectable or metastatic disease
- •No available treatment with curative intent
- •Adequate organ function
排除标准
- •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
- •Other active cancer
- •Cardiac abnormalities
研究组 & 干预措施
Phase 1 Dose Exploration
Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
干预措施: MRTX849 (Drug)
Phase 1 Dose Exploration
Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
干预措施: TNO155 (Drug)
Phase 1b Expansion
Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens
干预措施: MRTX849 (Drug)
Phase 1b Expansion
Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens
干预措施: TNO155 (Drug)
Phase 2
Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
干预措施: MRTX849 (Drug)
Phase 2
Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
干预措施: TNO155 (Drug)
结局指标
主要结局
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
时间窗: 20 months
Number of participants with treatment related adverse events
Evaluate the pharmacokinetics of MRTX849 and TNO155
时间窗: 20 months
Blood plasma concentration
次要结局
- Establish maximum tolerated dose(12 months)
- Evaluate clinical activity of MRTX849(20 months)