A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Anvumetostat in Subjects With Methylthioadenosine Phosphorylase (MTAP)-Deleted Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 61
- 试验地点
- 165
- 主要终点
- Objective Response (OR) per RECIST 1.1
研究概览
简要总结
The main objective of the study is to characterize safety and efficacy of 2 dose levels of anvumetostat by investigator, and to evaluate anvumetostat monotherapy efficacy by Blinded Independent Central Review (BICR).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically confirmed metastatic or unresectable locally advanced MTAP-deleted (Homozygous deletion of MTAP) NSCLC
- •Participants will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
- •Either an archival tissue sample or an archival block must be available.
- •Life expectancy of greater than 3 months, in the opinion of the investigator.
- •Participants who have had brain metastases and have been appropriately treated with radiation therapy or surgery ending at least 14 days before study day 1 are eligible.
- •Participants with untreated asymptomatic brain metastases smaller or equal to 2 cm in size (per lesion if more than one) and not requiring corticosteroid treatment are eligible.
排除标准
- •Disease Related
- •Tumors harboring the following mutations amenable to targeted therapies: epidermal growth factor receptor (EGFR), ALK receptor tyrosine kinase (ALK), ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), MET proto-oncogene (MET), B-Raf proto-oncogene (BRAF), RET proto-oncogene (RET), Human epidermal growth factor receptor 2 (HER2/ERBB2), KRAS proto-oncogene G12C (KRAS G12C).
- •Other Medical Conditions
- •Major surgery within 28 days of study day
- •Untreated symptomatic central nervous system (CNS) metastatic disease regardless of size or asymptomatic brain metastases greater than 2 cm per lesion.
结局指标
主要结局
Objective Response (OR) per RECIST 1.1
时间窗: Up to 35 months
Objective response (OR) Measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) and Assessed per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
时间窗: Up to 35 months
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 35 months
Number of Participants Experiencing Events of Interest (EOIs)
时间窗: Up to 35 months
Maximum Concentration (Cmax) of AMG 193
时间窗: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose
Time to Cmax (Tmax) of AMG 193
时间窗: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose
Area Under The Concentration-time Curve (AUC) of AMG 193
时间窗: Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose
次要结局
- Disease Control (DC) by BICR(Up to 35 months)
- Duration of Response (DOR) by BICR(Up to 35 months)
- Time to Response (TTR) by BICR(Up to 35 months)
- Progression-free Survival (PFS) by BICR(Up to 35 months)
- OR by Investigator's Assessment(Up to 35 months)
- DC by Investigator's Assessment(Up to 35 months)
- DOR by Investigator's Assessment(Up to 35 months)
- TTR by Investigator's Assessment(Up to 35 months)
- PFS by Investigator's Assessment(Up to 35 months)
- Overall Survival (OS)(Up to 35 months)
- Number of Participants Experiencing TEAEs(Up to 35 months)
- Cmax of AMG 193(Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose)
- Tmax of AMG 193(Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose)
- AUC of AMG 193(Cycle 1: Day 1 and Day 15 pre-dose, 0.5 hours, 1 hour, 2 hours, 4 hours, and 6 hours post-dose; Cycle 2: Day 1 and Day 15 pre-dose; Cycles 3-5: Day 1 pre-dose)
- Change in Quality of life (QoL) per The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ)-C30(Up to 12 months)
- Change in QoL per Quality of Life Questionnaire-Lung Cancer 13 (QLQ LC13)(Up to 12 months)
- Change in QoL per European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L)(Up to 12 months)
- Overall Health Status per Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 12 months)
- Overall Health Status per The Functional Assessment of Cancer Therapy - General (FACT-G)(Up to 12 months)