临床试验/NCT05975073

NCT05975073

已完成

1 期

A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Anvumetostat in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors

Amgen54 个研究点分布在 7 个国家目标入组 53 人2023年8月1日

适应症MTAP-null Non-Small-Cell Lung Cancer MTAP-null Solid Tumors

干预措施Anvumetostat IDE397

概览

阶段: 1 期
干预措施: Anvumetostat
疾病 / 适应症: MTAP-null Non-Small-Cell Lung Cancer
发起方: Amgen
入组人数: 53
试验地点: 54
主要终点: Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
状态: 已完成
最后更新: 10天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验相关资讯

概览

简要总结

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of Anvumetostat in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of anvumetostat in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

注册库

clinicaltrials.gov

开始日期

2023年8月1日

结束日期

2026年3月26日

最后更新

10天前

研究类型

Interventional

研究设计

Sequential

性别

All

研究者

发起方

Amgen

责任方

Sponsor

入排标准

入选标准

•Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.
•Presence of advanced/metastatic solid tumor not amenable to curative treatment
•Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists
•Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.
•Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product
•Disease measurable as defined by RECIST v1.1
•Adequate organ function as defined in the protocol.
•Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

排除标准

•Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
•Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease.
•Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
•Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis)
•History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
•Prior irradiation to \> 25% of the bone marrow
•Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product.

研究组 & 干预措施

Part 1: Dose Exploration of Anvumetostat Combined With IDE397

Participants will receive escalating doses of Anvumetostat and IDE397 administered orally (PO) in cycles of 21 days.

干预措施: Anvumetostat

Part 2: Dose Expansion of Anvumetostat Combined With IDE397

Anvumetostat and IDE397 will be administered PO in cycles of 21 days.

干预措施: Anvumetostat

Part 1: Dose Exploration of Anvumetostat Combined With IDE397

Participants will receive escalating doses of Anvumetostat and IDE397 administered orally (PO) in cycles of 21 days.

干预措施: IDE397

Part 2: Dose Expansion of Anvumetostat Combined With IDE397

Anvumetostat and IDE397 will be administered PO in cycles of 21 days.

干预措施: IDE397

结局指标

主要结局

Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

时间窗: Day 1 up to Day 21

Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

时间窗: Day 1 up to approximately 2.5 years

Any clinically significant changes in vital signs, electrocardiogram (ECG), or clinical laboratory test results will be recorded as adverse events

Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs)

时间窗: Day 1 up to approximately 2.5 years

Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

时间窗: Day 1 up to approximately 2.5 years

次要结局

Part 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of Anvumetostat(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of Anvumetostat(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Part 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Part 1 and 2: Cmax of IDE397(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Part 1 and 2: Tmax of IDE397(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of AMG 193(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: Area Under The Curve (AUC) After Multiple Doses of AMG 193(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: AUC After Single Dose of IDE397(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1 and 2: AUC After Multiple Doses of IDE397(Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
Parts 1: Overall Response per RECIST 1.1(Day 1 up to end-of-study (EOS) (approximately 2.5 years))
Parts 1 and 2: Disease Control Rate(Day 1 up to EOS (approximately 2.5 years))
Parts 1 and 2: Time to Response (TTR)(Day 1 up to EOS (approximately 2.5 years))
Parts 1 and 2: Duration of Response (DOR)(Day 1 up to EOS (approximately 2.5 years))
Parts 1 and 2: Duration of Stable Disease(Day 1 up to EOT (approximately 6 months))
Parts 1 and 2: Progression-free Survival (PFS)(Day 1 up to EOS (approximately 2.5 years))
Parts 1 and 2: Overall Survival (OS)(Day 1 up to EOS (approximately 2.5 years))
Part 2: Number of Participants Experiencing TEAEs(Day 1 up to approximately 2.5 years)
Part 2: Number of Participants Experiencing SAEs(Day 1 up to approximately 2.5 years)
Parts 1 and 2: Change From Baseline in Symmetric Dimethylation of Arginine (SDMA) in Blood(Baseline (Day 1) to EOT plus 30 days (approximately 7 months))