A Phase I, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of LT-010391 Tablets in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This study is to evaluate the safety and tolerability of of LT-010391 as monotherapy in participants with KRAS G12D mutant advanced solid tumors
详细描述
This is an open-label, multicenter, Phase 1 study of LT-010391, a selective and orally bioavailable KRAS G12D degrader in participants with KRAS G12D mutant advanced solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two parts: Part A- dose escalation and Part B- dose expansion.
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
- •Participants with histologically or cytologically confirmed advanced solid tumors harboring a KRAS G12D mutation;
- •Failed standard therapy, intolerant to standard therapy, or no standard therapy is available;
- •ECOG Performance Status of 0 or 1;
- •Adequate organ function
排除标准
- •History of ≥2 primary malignancies within 5 years prior to signing informed consent, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies considered cured;
- •Primary central nervous system (CNS) tumors
- •leptomeningeal metastases, brainstem metastases, or spinal cord compression confirmed by imaging (regardless of symptoms) Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
A single arm study of LT-010391 including dose-escalation and dose-expansion cohorts
Part A: Dose Escalation Participants will receive the designated dose. Enrollment into dose escalation may be from any advanced solid tumors with KRAS G12D mutation.
Part B: Dose Expansion:
Upon completing DLT observation for a dose level, investigators and sponsor may discuss selecting a specific cancer type for expansion at prior dose.
干预措施: LT-010391 (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to 2 years
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Dose Limiting Toxicities
时间窗: 21 days
Number of participants with Dose Limiting Toxicities (DLTs)
次要结局
- Pharmacokinetic parameters(up to 15 weeks)
- Overall Response Rate (ORR)(up to 2 years)
- Duration of Response (DOR)(up to 2 years)
- Disease Control Rate（DCR）(up to 2 years)
- Progression-Free Survival (PFS)(up to 2 years)