A Phase I Dose Finding Study of Oral LTT462 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
A phase I study of LTT462 in patients with advanced solid tumors that harbor MAPK pathway alterations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient (male or female) ≥12 years of age
- •ECOG (Eastern Cooperative Oncology Group) performance status ≤1
- •Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
- •Patients must be willing and able to undergo study required biopsies.
- •Presence of at least one measurable lesion according to RECIST v1.
- •Documented MAPK pathway alteration
排除标准
- •Prior treatment with ERK inhibitors.
- •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 malignant disease other than that being treated in the study.
- •Clinically significant cardiac disease.
- •Other protocol-defined exclusion criteria may apply.
研究组 & 干预措施
Escalation
干预措施: LTT462 (Drug)
Expansion Group 1
干预措施: LTT462 (Drug)
Expansion Group 2
干预措施: LTT462 (Drug)
Expansion Group 3
干预措施: LTT462 (Drug)
Expansion Group 4
干预措施: LTT462 (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 2.8 years
An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Percentage of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Up to 2.8 years
Percentage of participants with dose limiting toxicity were reported.
Percentage of Participants With at Least One Dose Reduction
时间窗: Up to 2.8 years
Percentage of participants with at least one dose reduction were reported.
Percentage of Participants With at Least One Dose Interruptions
时间窗: Up to 2.8 years
Percentage of participants with at least dose interruptions were reported.
Dose Intensity Received by Participants
时间窗: Up to 2.8 years
Dose intensity of LTT462 received by treatment group was reported.
次要结局
- Percentage of Participants With Overall Response Rate (ORR)(Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years))
- Percentage of Participants With Disease Control Rate (DCR)(Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years))
- Duration of Response (DOR)(Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years))
- Progression Free Survival (PFS)(Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years))
- Overall Survival (OS) - Only for Dose Expansion Phase(Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years))
- The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462(day 1, day 15)
- Elimination Half-life (T1/2) of LTT462(Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462(Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462(day 1, day 15)
- Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462(Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Accumulation Ratio (Racc) of LTT462(Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood(Cycle 1 Days 1, 2, 3, 15 and 16)