A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 731
- 试验地点
- 444
- 主要终点
- Characterize the safety of MRTX849 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 (adagrasib) 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 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.
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
- •Unresectable or metastatic disease
- •Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts
- •Adequate organ function
排除标准
- •History of intestinal disease or major gastric surgery or inability to swallow oral medications
- •Other active cancer
研究组 & 干预措施
Pilot Phase 1b Combination with Pembrolizumab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC
干预措施: Pembrolizumab (Drug)
Phase 2 Combination with Cetuximab
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Cetuximab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC
干预措施: Cetuximab (Drug)
Phase 2 Combination with Cetuximab
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
干预措施: Cetuximab (Drug)
Pilot Phase 1b Combination with Cetuximab in PDAC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Cetuximab in NSCLC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC
干预措施: Cetuximab (Drug)
Pilot Phase 1b Combination with Pembrolizumab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Cetuximab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC
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 to recommend Phase 2 regimens
干预措施: MRTX849 (Drug)
Phase 2
Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849
干预措施: MRTX849 (Drug)
Phase 1 Dose Exploration
Dose escalation of MRTX849 to determine maximum tolerated dose
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Afatinib
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Cetuximab in NSCLC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC
干预措施: MRTX849 (Drug)
Pilot Phase 1b Combination with Afatinib
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC
干预措施: Afatinib (Drug)
Pilot Phase 1b Combination with Cetuximab in PDAC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)
干预措施: Cetuximab (Drug)
结局指标
主要结局
Characterize the safety of MRTX849 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
时间窗: 20 months
Blood plasma concentration
Evaluate clinical activity/efficacy of MRTX849
时间窗: 20 months
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
次要结局
- Establish maximum tolerated dose(12 months)
- Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents(12 months)
- Evaluate the pharmacokinetics of new MRTX849 oral formulations(6 months)
- Evaluate the pharmacokinetics of MRTX849 administered with food(6 months)