A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 199 in Subjects With MUC17-Positive Solid Tumors Including Gastric, Gastroesophageal Junction, Colorectal, and Pancreatic Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 58
- 试验地点
- 21
- 主要终点
- Incidence of Treatment-related adverse events (TRAEs)
研究概览
简要总结
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
详细描述
AMG 199 is a novel half-life extended (HLE) bispecific T cell engager (BiTE®) molecule designed to direct T cells towards MUC17-expressing cells. This is a first-in-human study in adult subjects with MUC17-positive solid tumors including gastric cancer, gastroesophageal junction (GEJ), colorectal, and pancreatic cancers, collectively referred to as "solid tumors" in this clinical investigation to assess AMG 199 safety, tolerability, pharmacokinetics (PK), and anti-tumor activity, with additional exploratory objectives to assess pharmacodynamics (PD), correlative biomarker analysis, and immunogenicity.
The primary end point is to evaluate the safety and tolerability of AMG 199 in adult subjects, and determine the MTD and RP2D. The secondary end point is characterize the PK and anti-tumor activity of AMG 199.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Key Inclusion Criteria:
- •Subjects with histologically or cytologically confirmed metastatic or locally advanced unresectable gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma positive for MUC
- •Subjects should have been refractory to or have relapsed after two or more prior lines of standard systemic therapy that included a platinum, a fluoropyrimidine, nivolumab (in combination with a platinum and a fluoropyrimidine), either a taxane or irinotecan, and an approved vascular endothelial growth factor receptor (VEGFR) antibody/tyrosine kinase inhibitor (TKI).
- •Subjects with histologically or cytologically confirmed metastatic or locally advanced unresectable colorectal cancer positive for MUC
- •Subjects should have been refractory to or have relapsed after at least two and up to five prior lines of standard systemic therapy. Therapy should have included an approved vascular endothelial growth factor (VEGF) antibody (if clinically appropriate) and epidermal growth factor receptor (EGFR) antibody (if kirsten rat sarcoma [KRAS]/ neuroblastoma RAS viral oncogene homolog [NRAS]/ v-Raf murine sarcoma viral oncogene homolog B1 [BRAF] wild type tumor).
- •Subjects with histologically or cytologically confirmed unresectable or metastatic pancreatic ductal adenocarcinoma positive for MUC
- •Subjects should have been refractory to or have relapsed after at least one and up to three prior lines of standard systemic therapy.
- •Gastric adenocarcinoma and GEJ adenocarcinoma: Subjects eligible for human epidermal growth factor receptor 2 (HER2) directed therapy, prior systemic therapy should have an approved HER2 targeting antibody approved for treatment of gastric cancer. For subjects with microsatellite instability high (MSI H) or mismatch repair deficient (dMMR) tumors a prior line of treatment should have included an approved programmed cell death protein-1 (PD-1) blocking antibody.
- •Colorectal cancer: For subjects with MSI H or dMMR tumors a prior line of treatment should have included an approved PD-1-blocking antibody. For subjects with BRAF V600E mutation positive tumors a prior line of treatment should have included a BRAF inhibitor.
- •Subjects may also be included if the aforementioned therapeutic options were medically not appropriate for them. In these cases, the reason(s) why required prior therapies for solid tumors were medically not appropriate should be documented in the subject's electronic case report form (eCRF). Subjects may also be included if the aforementioned therapeutic options have not been available or accessible for them.
- •For dose expansion only: Subjects with at least one measurable lesion ≥ 10mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study.
排除标准
- •Key Exclusion Criteria:
- •Any anticancer therapy or immunotherapy within 4 weeks of start of first dose.
- •Central nervous system (CNS) metastases, leptomeningeal, or spinal cord compression.
- •Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy. Subjects may be included if the treatment is discontinued more than 3 months prior to the first dose of AMG 199, there is a low likelihood of relapse from the autoimmune disorder, AND there is agreement between the investigator and the Amgen Medical Monitor.
研究组 & 干预措施
Dose-exploration phase
The dose-exploration phase of the study will estimate the MTD (Maximum Tolerated Dose) of AMG 199 using a Bayesian logistic regression model (BLRM). A RP2D (Recommended Phase 2 Dose) may be identified based on emerging safety, efficacy, and PD (Pharmacodynamics) data prior to reaching an MTD. Alternative dosing schedule(s) may be explored based on emerging PK (Pharmacokinetics) and safety data.
干预措施: AMG 199 (Drug)
Dose-expansion phase
The dose-expansion phase will be conducted to confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and enable correlative biomarker analysis.
干预措施: AMG 199 (Drug)
结局指标
主要结局
Incidence of Treatment-related adverse events (TRAEs)
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Incidence of Dose-limiting toxicities (DLT)
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Incidence of Treatment-emergent adverse events (TEAEs)
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Number of subjects with changes in vital signs
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Number of subjects with changes in clinical laboratory tests
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Number of subjects with changes in electrocardiogram (ECG)
时间窗: 3 years
To evaluate the safety and tolerability of AMG 199 in adult subjects and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
次要结局
- Duration of response (DOR).(3 years)
- Time to progression (TTP)(3 years)
- Progression-free survival (PFS), 1-year PFS(1 year)
- Area under the concentration-time curve (AUC) of AMG 199(3 years)
- Accumulation following multiple dosing of AMG 199(3 years)
- Half-life (t1/2) of AMG 199(3 years)
- Overall survival (OS), 2-year OS(2 years)
- Maximum serum concentration (Cmax) of AMG 199(3 years)
- Overall survival (OS), 1-year OS.(1 year)
- Progression-free survival (PFS), 6-month PFS(6 months)
- Minimum serum concentration (Cmin) of AMG 199(3 years)
- Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST.(3 years)