A Study of PARG Inhibitor IDE161 in 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
- 216
- 试验地点
- 37
- 主要终点
- Part 1 (Dose Escalation): To characterize the safety and tolerability of IDE161 monotherapy or in combination with pembrolizumab to determine the MTD and/or RDE
研究概览
简要总结
The purpose of this study is to characterize the safety, tolerability, and efficacy of IDE161 as a single agent and in combination with pembrolizumab.
详细描述
The purpose of this study is to characterize the safety, tolerability including determination of maximum tolerated dose (MTD), maximum accepted dose (MAD), recommended dose(s) for expansion (RDE) and/or recommended Phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of IDE161 as a single agent in participants with advanced or metastatic solid tumors harboring BRCA1/2 loss of function alterations and/or other defects in the homologous recombination (HR) pathway and in combination with pembrolizumab in participants with advanced/recurrent endometrial cancer.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants must be 18 years of age or older
- •Advanced or metastatic solid tumors excluding primary central nervous system (CNS) tumors
- •For Module 1 only, Have documented evidence of BRCA1/2 and/or genetic alterations conferring homologous recombination deficiency (HRD) (ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L, NBN, FANCA)
- •For Module 2 only, results of MSI and/or MMR testing required.
- •For Module 2 only, results of BRCA1/2 and HRD gene testing required.
- •Participant must have progressed on at least one prior line of therapy in the advanced or metastatic setting that is considered an appropriate standard of care, or for which the participant has documented intolerance
- •For Module 2 only, advanced or metastatic Endometrial Cancer (uterine carcinosarcoma is excluded)
- •For Module 2 only, Must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (MAB)
排除标准
- •Known primary CNS malignancy
- •Impairment of GI function or GI disease that may significantly alter the absorption of IDE161
- •Have active, uncontrolled infection
- •Clinically significant cardiac abnormalities
- •Major surgery within 4 weeks prior to enrollment
- •Radiation therapy within 2 weeks prior to enrollment
- •Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment
- •Radioimmunotherapy within 6 weeks of enrollment
- •Treatment with a therapeutic antibody within 4 weeks prior to enrollment
- •Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks, whichever is shorter
- •Have current active liver or biliary disease
- •For Module 2 only, History or allogeneic tissue/solid organ transplant
- •For Module 2 only, Active autoimmune disease that has required systemic treatment in past 2 years
- •For Module 2 only, History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
研究组 & 干预措施
Module 2 Part 2: Combination Dose Expansion with pembrolizumab
After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
干预措施: Pembrolizumab (Drug)
Module 2 Part 2: Combination Dose Expansion with pembrolizumab
After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
干预措施: IDE-161 (Drug)
Module 2 Part 1: Combination Dose Escalation with pembrolizumab
Participants will be assigned to a dose level.
干预措施: Pembrolizumab (Drug)
Module 1 Part 2: Monotherapy Dose Expansion
After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
干预措施: IDE-161 (Drug)
Module 2 Part 1: Combination Dose Escalation with pembrolizumab
Participants will be assigned to a dose level.
干预措施: IDE-161 (Drug)
Module 1 Part 1: Monotherapy Dose Escalation
Participants will be assigned to a dose level.
干预措施: IDE-161 (Drug)
结局指标
主要结局
Part 1 (Dose Escalation): To characterize the safety and tolerability of IDE161 monotherapy or in combination with pembrolizumab to determine the MTD and/or RDE
时间窗: Approximately 2 years
* Incidence of Dose Limiting Toxicities * Incidence of treatment-emergent Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy * Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
Part 2 (Dose Expansion): To further assess the safety and tolerability of IDE monotherapy and in combination with pembrolizumab at the RDE
时间窗: Approximately 4 years
* Incidence of treatment-emergent AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy * Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing
Part 2 (Dose Expansion): To evaluate preliminary anti-tumor activity of IDE161 monotherapy or in combination with pembrolizumab
时间窗: Approximately 4 years
Tumor response: Overall Response Rate assessed using RECIST criteria v1.1
次要结局
- Part 2 (Dose Expansion) Assess the risk/benefit at an IDE161 monotherapy dose and exposure alternative to the initial expansion dose; as well as an IDE161 dose in combination with a fixed dose of pembrolizumab and exposure alternative to the initial(Approximately 4 years)
- To characterize the single dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)
- To characterize the multiple dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)
- To characterize the single dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)
- To characterize the multiple dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)
- To characterize the single dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)
- To characterize the multiple dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.(Approximately 4 years)