A Phase 1/2, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 in Subjects With Advanced or Metastatic Solid Tumors With KRasG12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Subject incidence of Dose-limiting toxicities (DLT)
研究概览
简要总结
This is a phase 1/2, open label study of D-1553 single agent and combination treatment to assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and antitumor activities in subjects with advanced or metastatic solid tumor with KRasG12C mutation.
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
- 未提供
排除标准
- •Subject with unstable or progressive central nervous system (CNS) metastases.
- •Subject with acute myocardial infarction, severe/unstable angina; or with cardiac insufficiency of New York Heart Association Functional Classification Grade 2 or above.
- •Subject has corrected QT interval using Fridericia's formula (QTcF) prolongation at rest, where the mean QTc interval is > 480 msec based on triplicate measurements of electrocardiogram (ECG).
- •Subject with stroke or other severe cerebrovascular diseases within 12 months before enrollment;
- •Subject with interstitial lung disease or acute lung infection not yet recovered including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection;
- •Subject has any history or evidence of substance abuse or medical, psychological or social conditions that may, in the opinion of the investigator, interfere with participation in the study or evaluation of the study results.
- •Subject has impaired gastrointestinal (GI) function or GI diseases that may significantly alter the absorption or metabolism of oral medications.
- •Subject has unresolved toxicities from prior anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE, v5.0, Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy).
- •Subject had major surgery within 4 weeks prior to study intervention administration or last dose of palliative radiation therapy within 2 weeks prior to study intervention administration.
- •Subject is pregnant or lactating.
研究组 & 干预措施
Dose escalation of D-1553 monotherapy
Phase 1a will evaluate up to 7 sequential cohorts with different doses of D-1553 to determine safety, tolerability, MTD and RDE in patients with solid tumors with KRasG12C mutation.
干预措施: D-1553 (Drug)
Dose combination of D-1553 with other therapies
Phase 1b will determine the MTD of D-1553 in combination treatment in subjects with advanced or metastatic NSCLC, CRC and other solid tumors. There are multiple groups in Phase 1b for different tumor types and treatment combinations to evaluate safety, MTD and RP2D.
干预措施: D-1553 (Drug)
Phase 2 of D-1553 monotherapy and combination therapies
The Phase 2 portion is a multi-arm, parallel, open label study to evaluate the efficacy of D- 1553 single agent and combination treatments in subjects with advanced or metastatic solid tumors with KRas G12C mutation. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose.
干预措施: D-1553 (Drug)
结局指标
主要结局
Subject incidence of Dose-limiting toxicities (DLT)
时间窗: through out the DLT period, approximately 21 days
Number of subjects participants with adverse events
时间窗: Through study completion, approximately 3 years
Plasma concentration of D-1553 as a single agent or in combination with other therapies in subjects wiht advanced or metastatic solid tumors with KRas G12C mutation.
时间窗: Through study completion, approximately 3 years
次要结局
未报告次要终点