An Open Label, Phase 1, Treatment Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of IDE397 (MAT2A Inhibitor) In Adult Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 169
- 试验地点
- 71
- 主要终点
- To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms
研究概览
简要总结
This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397 as a single agent and in combination with sacituzumab govitecan (SG), in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Participant must be at least 18 years of age
- •Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy
- •Have evidence of homozygous loss of MTAP or MTAP deletion
- •Willing to undergo paired fresh biopsy (pre- and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns
- •Measurable disease
- •ECOG performance status <= 1
- •Adequate organ function
- •Able to swallow and retain orally administered study treatment
- •Recovery from acute effects of prior therapy
- •Able to comply with contraceptive/barrier requirements
排除标准
- •Known symptomatic brain metastases
- •Known primary CNS malignancy
- •Current active liver or biliary disease
- •Impairment of gastrointestinal (GI) function
- •Active uncontrolled infection
- •Clinically significant cardiac abnormalities
- •Active second malignancy or history of another malignancy in the past 2 years
- •Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor or sacituzumab govitecan
- •Systemic anti-cancer therapy, therapeutic antibody treatment, or major surgery within 4 weeks prior to study entry
- •Current radiation-related toxicity or radiation therapy within 2 weeks prior to study entry
- •Small molecule anti-cancer treatment within 2 weeks prior to study entry
- •Prior irradiation to >25% of the bone marrow
- •Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers
- •Require concomitant use of proton pump inhibitor
- •Currently receiving another investigational study drug.
- •Known or suspected hypersensitivity to IDE397/excipients or components
研究组 & 干预措施
Part 2: Monotherapy Dose Expansion (NSCLC and Urothelial)
干预措施: IDE397 (Drug)
Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (NSCLC and Urothelial)
干预措施: IDE397 (Drug)
Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (NSCLC and Urothelial)
干预措施: Sacituzumab govitecan (Drug)
Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (NSCLC and Urothelial)
干预措施: IDE397 (Drug)
Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (NSCLC and Urothelial)
干预措施: Sacituzumab govitecan (Drug)
Part 1: Dose Escalation Monotherapy (Solid Tumors)
干预措施: IDE397 (Drug)
结局指标
主要结局
To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms
时间窗: Approximately 2 years
Objective Response Rate (ORR) and Duration of Response (DoR)
Dose-limiting Toxicities (DLTs) of IDE397
时间窗: 21 days following the first dose of IDE397
Incidence of DLTs of IDE397 will be determined
Dose-limiting Toxicities (DLTs) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan
时间窗: 21 - 28 days following the first dose of IDE397
Incidence of DLTs of IDE397 in a combination setting will be determined
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397
时间窗: Approximately 2 years
MTD and RP2D of IDE397 will be determined
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan
时间窗: Approximately 2 years
MTD and RP2D of IDE397 in a combination setting will be determined
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with sacituzumab govitecan
时间窗: Approximately 2 years
MTD and RP2D of IDE397 in a combination setting will be determined
Dose-limiting Toxicities (DLTs) of IDE397 in combination with sacituzumab govitecan
时间窗: 21 - 28 days following the first dose of IDE397
Incidence of DLTs of IDE397 in a combination setting will be determined
To evaluate preliminary anti-tumor activity of IDE397 as monotherapy and in combination with sacituzumab govitecan-hziy in expansion arms
时间窗: Approximately 2 years
Objective Response Rate (ORR) and Duration of Response (DoR)
次要结局
- Pharmacodynamic effect of IDE397 as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan(Approximately 2 years)
- Preliminary anti-tumor activity in IDE397 escalation and combination escalation arms(Approximately 2 years)
- Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan(Approximately 2 years)
- Plasma Pharmacokinetics of IDE397 and metabolite(Approximately 2 years)
- Drug interaction between IDE397 and sacituzumab govitecan(Approximately 2 years)
- Pharmacodynamic effect of IDE397 as a single agent and in combination with sacituzumab govitecan(Approximately 2 years)