A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- Part 1: Dose-limiting toxicities, certain treatment related side effects that can occur in the first cycle of treatment. Adverse events (side effects) that occur after the start of treatment, or are related to treatment, or require significant intervention. Changes in vital signs (including blood pressure, heart rate, respiratory rate, and temperature), electrocardiograms, and clinical laboratory tests
研究概览
简要总结
Part 1: To study the maximum tolerated dose (MTD; the highest dose of the study drugs in combination which is safe to take and tolerated) or recommended dose of AMG 193 in combination with IDE397 in adult participants with locally advanced or metastatic MTAP-null solid tumors Part 2: To study the anti-cancer activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non Small Cell Lung Cancer (NSCLC).
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Experimental: Part 1: Dose exploration of AMG 193 combined with IDE397
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
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. For Part 1, MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists. For 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
结局指标
主要结局
Part 1: Dose-limiting toxicities, certain treatment related side effects that can occur in the first cycle of treatment. Adverse events (side effects) that occur after the start of treatment, or are related to treatment, or require significant intervention. Changes in vital signs (including blood pressure, heart rate, respiratory rate, and temperature), electrocardiograms, and clinical laboratory tests
Part 1: Dose-limiting toxicities, certain treatment related side effects that can occur in the first cycle of treatment. Adverse events (side effects) that occur after the start of treatment, or are related to treatment, or require significant intervention. Changes in vital signs (including blood pressure, heart rate, respiratory rate, and temperature), electrocardiograms, and clinical laboratory tests
Part 2: Whether the cancer responds to treatment, either a complete or a partial improvement of cancer lesions, as assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). RECIST is a scale set of rules used to determine if classify how a cancer patient is responding to treatment.
Part 2: Whether the cancer responds to treatment, either a complete or a partial improvement of cancer lesions, as assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). RECIST is a scale set of rules used to determine if classify how a cancer patient is responding to treatment.
次要结局
- Blood levels of AMG 193 and IDE397 when given in combination, including, but not limited to, maximal plasma concentration (Cmax) - that is the maximum amount of study drug present in the blood plasma, time to maximal plasma concentration (tmax) - that is the time required to achieve the maximum plasma concentration, and total drug levels over time.
- The proportion of treated patients who respond to treatment by looking at tumor shrinkage or growth over time as assessed by CT or MRI imaging; the duration of time a tumor responds or does not increase in size while on study treatment; progression free survival (PFS) and overall survival (OS).
- Part 2: Treatment emergent adverse events, serious adverse events, and changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests
- Changes in blood levels of SDMA over time.
研究者
Medical Information
Scientific
Amgen Inc.