A Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of NB004 Administered as Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 6
- 主要终点
- Incidence of adverse events----Part 1/2
研究概览
简要总结
This is a Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of NB004 Administered as Monotherapy or Combination Therapy in Subjects with Advanced Solid Tumors
详细描述
This study is a Phase 1, open-label, multicenter study of NB004 administered orally in patients with histologically and/or cytologically confirmed diagnosis of advanced solid tumors that are metastatic for which all standard treatment options have been given and are ineffective, or is no longer eligible for additional standard treatment options.
The study is comprised of a dose escalation phase to determine the maximum tolerated dose and the RP2D and an expansion phase to further explore the safety and preliminary antitumor activity of NB004.
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
- •males or females of any race>(=)18 years age.
- •Histologically and/or cytologically confirmed diagnosis of advanced solid tumors that are without standard treatment options (part 1).
- •Pathologically confirmed locally advanced or metastatic solid tumors with KRAS G12C mutation as determined by a test that has been approved by FDA or local health authority (part 2&3).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy>(=)12 weeks.
- •Adequate organ and marrow function.
- •Measurable or evaluable disease.
排除标准
- •Prior anti-cancer therapy within 2 weeks or at least 5 half-lives, whichever is longer, up to a maximum of 3 weeks, before the first dose.
- •Toxicities from previous anti-cancer therapy that have not recovered as required.
- •Brain metastatic disease, spinal cord compression, or leptomeningeal carcinomatosis.
- •Active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV):
- •Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while in this study or within 3 months after the last dose.
- •Male subjects who plan to father a child while enrolled in the study or within 3 months after the last dose.
- •Received prior treatment with a PIM kinase inhibitor.
研究组 & 干预措施
NB004
Part1: Dose escalation phase of study drug NB004 monotherapy:
Part 2: Dose Escalation Phase for the NB004 in combination with Sotorasib:
Part 3: COMBO Dose Expansion Phase for the NB004 in combination with Sotorasib:
干预措施: NB004 tablets (Drug)
结局指标
主要结局
Incidence of adverse events----Part 1/2
时间窗: Approximately 24 months since the first subject enrolled
An adverse event is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.
Duration of Response (DOR) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
DOR is defined as the time from the date of first documented response until date of documented progression, for subjects who achieve CR or PR.
Clinical Benefit Rate (CBR) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
CBR is defined as the number of subjects with CR or PR or with SD maintained ≥24 weeks (as assessed by the Investigator, using RECIST v1.1) divided by the number of subjects in the analysis. Subjects without a postbaseline tumor assessment will be considered as having no clinical benefit.
Incidence of dose-limiting toxicities----Part 1/2
时间窗: When subject complete 1 cycle (28 days) treatment with safety and tolerability assessment by investigators.
Dose-limiting toxicities will be reviewed as a subset of adverse events that occurs within the first 28 days of dosing and meet protocol-specified criteria.
Objective Response Rate (ORR) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
Objective Response Rate (ORR) is defined as the percentage of patients whose efficacy is confirmed as complete response (CR) or partial response (PR)
Time to Response (TTR) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
TTR is defined as the time interval between the date of first administration and the date of the first recording of response. At the same time, the initial response time and the time to best response will be calculated.
Progression-free Survival (PFS) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
PFS is defined as the time from the date of the first dose until the date of disease progression, as defined by RECIST v1.1, or death.
Overall survival (OS) ----Part 3
时间窗: [Time Frame: Approximately 24 months since the first subject enrolled]
OS is defined as the time from treatment start with study drug until event of death due to any cause.
次要结局
- Terminal elimination half life----Part 1(Approximately 24 months since the first subject enrolled)
- Objective Response Rate (ORR)----Part 2(Approximately 24 months since the first subject enrolled)
- Maximum observed plasma concentration (Cmax)----Part 1(Approximately 24 months since the first subject enrolled)
- Clinical Benefit Rate (CBR) ----Part 2([Time Frame: Approximately 24 months since the first subject enrolled])
- Time to Cmax (Tmax)----Part 1(Approximately 24 months since the first subject enrolled)
- Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t) ----Part 1(Approximately 24 months since the first subject enrolled)
- Overall survival (OS) ----Part 2([Time Frame: Approximately 24 months since the first subject enrolled])
- Duration of Response(DOR)----Part 2(Approximately 24 months since the first subject enrolled)
- Time to Response (TTR) ----Part 2([Time Frame: Approximately 24 months since the first subject enrolled])
- Progression-free Survival (PFS) ----Part 2([Time Frame: Approximately 24 months since the first subject enrolled])