A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 232
- 试验地点
- 23
- 主要终点
- To determine the maximally tolerated dose (MTD)
研究概览
简要总结
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.
详细描述
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
- •Biomarker-selected solid tumors
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
- •Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
- •Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
排除标准
- •Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
- •Requirement of pharmacologic doses of glucocorticoids
- •Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
- •HIV positive; known active hepatitis B or C
- •Known hypersensitivity to any of the components of PRT543
- •Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
研究组 & 干预措施
PRT543
PRT543 will be administered orally
干预措施: PRT543 (Drug)
结局指标
主要结局
To determine the maximally tolerated dose (MTD)
时间窗: Baseline through approximately 2 years.
The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
To describe dose limiting toxicities (DLT) of PRT543
时间窗: Baseline through Day 28.
Dose limiting toxicities (DLTs) will be evaluated during the first cycle
To determine the recommended phase 2 dose (RP2D) and schedule of PRT543
时间窗: Baseline through approximately 2 years.
The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
次要结局
- To describe the adverse event profile and tolerability of PRT543(Baseline through approximately 2 years)
- To determine the maximum observed plasma concentration (Cmax) of PRT543(Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.)
- To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543(Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.)