A Phase 1b/2 Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 6
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
A Phase 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
详细描述
Phase 1 Dose Escalation: To evaluate tolerability of repotrectinib at increasing dose levels in combination with other anticancer therapies for the treatment of subjects with locally advanced or metastatic KRAS-mutant solid tumors
Phase 2 Efficacy Evaluation: Investigate the anti-tumor efficacy and safety of repotrectinib in combination with other anticancer therapies for the treatment of patients with locally advanced or metastatic KRAS-mutant solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Age ≥ 18 (or as required by local regulation).
- •Histological or cytological confirmation of unresectable or metastatic solid tumor malignancy harboring a KRAS mutation.
- •No more than 3 prior standard treatments appropriate for tumor type and stage of disease.
- •ECOG performance status ≤
- •Existence of measurable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
- •Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
- •Adequate organ function.
排除标准
- •Major surgery within four weeks of the start of treatment.
- •Previous other cancer requiring treatment within the previous two years.
- •Clinically significant cardiovascular disease.
- •Any of the following cardiac criteria:
- •Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events
- •Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
- •Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
- •Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
- •Subjects being treated with or anticipating the need for treatment with strong CYP3A inhibitors or inducers.
研究组 & 干预措施
TPX-0005 + Trametinib
TPX-0005 + Trametinib Dose Escalation and Dose Expansion
Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC
干预措施: TPX-0005 (Drug)
TPX-0005 + Trametinib
TPX-0005 + Trametinib Dose Escalation and Dose Expansion
Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC
干预措施: Trametinib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: From initial dose to end of first cycle of treatment, approximately 28 days
Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D. A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol. The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1).
次要结局
- Tmax of Repotrecitinib(At Cycle 1 Day 1 and Cycle 1 Day 22)
- Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.(From screening to end of treatment approximately 10 months)
- Cmax of Repotrectinib(At Cycle 1 Day 1 and Cycle 1 Day 22)
- AUC 0-24 of Repotrecitinib(At Cycle 1 Day 1 and Cycle 1 Day 22)
- Cmax of Trametinib(At Cycle 1 Day 1 and Cycle 1 Day 22)
- Tmax of Trametinib(At Cycle 1 Day 1 and Cycle 1 Day 22)
- AUC 0-24 of Trametinib(At Cycle 1 Day 1 and Cycle 1 Day 22)