A Phase 1/1b Dose Escalation/Expansion Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 71
- 试验地点
- 6
- 主要终点
- Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
研究概览
简要总结
Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors
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
- •Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy.
- •Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for their tumor type for which the patient was eligible and willing to receive.
- •Adequate bone marrow, kidney and liver function
- •Performance status of 0 or
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for AEs not constituting a safety risk by Investigator judgement.
排除标准
- •Prior treatment targeting LAIR1
研究组 & 干预措施
NGM438 Monotherapy Dose Escalation
Part 1a Single Agent Dose Escalation
干预措施: NGM438 (Drug)
NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® )
Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )
干预措施: NGM438 (Drug)
NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® )
Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )
干预措施: Pembrolizumab (KEYTRUDA ®) (Drug)
Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®)
Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )
干预措施: NGM438 (Drug)
Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®)
Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )
干预措施: Pembrolizumab (KEYTRUDA ®) (Drug)
结局指标
主要结局
Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
时间窗: Baseline up to 15 days
Changes in potential pharmacodynamic biomarker CD163 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD163
时间窗: Baseline up to 15 days
Number of Patients with Adverse Events
时间窗: Approximately 24 months
Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug. An AE is defined as any untoward medical occurrence in a patient, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of patients who experience at least one AE will be presented.
Number of Patients with Dose-limiting Toxicities
时间窗: Baseline up to 21 Days
A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 5.0, and is considered by the Investigator to be clinically relevant and attributed to the study treatment during the first 21 days after the first dose of study treatment.
Number of Patients with Clinically Significant Laboratory Abnormalities
时间窗: Approximately 24 months
Number of patients with clinically significant change from baseline in laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE version 5.0) and timing.
Changes in potential pharmacodynamic biomarker CD8 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD8
时间窗: Baseline up to 15 days
次要结局
- Systemic Clearance (CL) of NGM438(Approximately 24 months. Each Cycle is 21 days.)
- Volume of Distribution (Vss) of NGM438 at Steady State(Approximately 24 months. Each Cycle is 21 days.)
- Anti-drug Antibodies (ADA) Against NGM438(Approximately 24 months. Each Cycle is 21 days.)
- Trough Concentrations of NGM438 in Patients in the Biopsy Cohort(Approximately 24 months. Each Cycle is 21 days.)
- Maximum Observed Serum Concentration (Cmax) of NGM438(Approximately 24 months. Each Cycle is 21 days.)
- Time to Maximum (Tmax) Observed Serum Concentration of NGM438(Approximately 24 months. Each Cycle is 21 days.)
- Area Under the Curve (AUC) of Serum NGM438(Approximately 24 months. Each Cycle is 21 days.)
- Half-life (t1/2) of NGM438 in Serum(Approximately 24 months. Each Cycle is 21 days.)
- Number of Patients in Dose Escalation and Dose Finding Cohorts with Objective Responses(Approximately 24 months)