NCT02974725终止1 期
A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 241
- 试验地点
- 7
- 主要终点
- Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
研究概览
简要总结
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients must have advanced or metastatic NSCLC or cutaneous melanoma
- •Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
- •All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
- •ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
排除标准
- •Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).
- •Patients who have received more than 3 lines of anti-cancer therapy are excluded.
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- •Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- •Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- •Patients with Gilbert's syndrome or other heritable diseases of bile processing.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LXH254+LTT462
Experimental
干预措施: LXH254 (Drug)
LXH254+LTT462
Experimental
干预措施: LTT462 (Drug)
LXH254+Trametinib
Experimental
干预措施: LXH254 (Drug)
LXH254+Trametinib
Experimental
干预措施: Trametinib (Drug)
LXH254+Ribociclib
Experimental
干预措施: LXH254 (Drug)
LXH254+Ribociclib
Experimental
干预措施: Ribociclib (Drug)
结局指标
主要结局
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
时间窗: up to 5 years
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
时间窗: up to 5 years
Dose limiting toxicities (DLTs) (dose escalation only)
时间窗: up to 3 years
Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity
时间窗: Up to 5 years
次要结局
- Overall Response Rate (ORR)(Up to 5 years)
- Progression Free Survival (PFS)(Up to 5 years)
- Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples(up to 5 years)
- Derived PK parameter (AUC) for LXH254 & ribociclib(Up to 5 years)
- Duration of response (DOR)(Up to 5 years)
- Derived PK parameter (AUC) for LXH254 & LTT462(Up to 5 years)
- Disease Control Rate (DCR)(Up to 5 years)
- Overall Survival (OS) - (dose expansion part only)(Up to 5 years)
- Derived PK parameter (Cmax) for LXH254 & LTT462:(Up to 5 years)
- Derived PK parameter (AUC) for LXH254 & trametinib(Up to 5 years)
- Derived PK parameter (Cmax) for LXH254 & trametinib(up to 5 years)
- Derived PK parameter (Cmax) for LXH254 & ribociclib(Up to 5 years)
研究者
研究点 (7)
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