A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
研究概览
简要总结
ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies [Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other NHL subtypes).
详细描述
The ZX-101A-101 study will consist of 2 parts:
- Part 1: ZX-101A Dose Escalation
- Part 2: ZX-101A Dose Expansion
The Part 1 (dose escalation) of the study is designed to determine the safety and tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose expansion) of the study is designed to further investigate the safety, tolerability, pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).
Results of clinical findings in patients in the dose-escalation portion of the study will be reviewed to identify conditions (or genetic characteristics) most likely to respond to ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the dose-expansion part of the study.
Male or female patients who are 18 years of age or older with relapsed/resistant or refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be included in the study provided that all inclusion and exclusion criteria are satisfied.
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
- •Males and females who are ≥ 18 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •Failed at least 2 prior systemic standard therapies.
- •Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes.
- •Documented active disease that is relapsed/resistant or refractory requiring treatment after established therapy shown to have clinical benefit.
- •Acceptable bone marrow, kidney, and liver function.
- •No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment.
- •Ability to swallow and retain oral medications (see exclusion criteria #20 below).
- •Negative serum pregnancy test in women of childbearing potential at Screening.
- •Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use effective contraceptive methods.
- •Men must agree to no sperm donations during the study and for 3 months after the last dose of ZX-101A.
- •Understands the requirements of the study (e.g. periodic imaging studies, periodic blood sampling, bone marrow studies), is willing to comply with all study procedures and signed the Institutional Review Board (IRB)-approved informed consent.
排除标准
- •Received investigational study drug within 28 days (or 5 half-lives, whichever is longer).
- •Concurrent participation in another therapeutic treatment trial.
- •Received approved anti-cancer drugs within 21 days (42 days for nitrosoureas) or 5 half-lives, whichever is longer.
- •Ongoing immunosuppression for chronic conditions.
- •Known active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.
- •Any concurrent uncontrolled illness.
- •Has not recovered from adverse events from prior anti-cancer treatment (with exception of alopecia).
- •Pregnant or breast-feeding or planning to conceive or father children within the projected duration of the study.
- •Major surgery within 4 weeks prior to first dose of study treatment.
- •Radiation treatment within 2 weeks prior to first dose of study treatment.
- •Gastrointestinal dysfunction, including motility or malabsorption syndromes or inflammatory bowel disease which could limit absorption of study drug.
- •Active or prior pneumonitis or interstitial lung disease.
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
ZX-101A Dose Level 1
Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
干预措施: ZX-101A (Drug)
ZX-101A Dose Level 2
2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
干预措施: ZX-101A (Drug)
ZX-101A Dose Level 3
3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
干预措施: ZX-101A (Drug)
ZX-101A Dose Level 4
4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
干预措施: ZX-101A (Drug)
ZX-101A Dose Level 5
5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
干预措施: ZX-101A (Drug)
结局指标
主要结局
Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
时间窗: From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.
To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
Safety and tolerability of ZX-101A
时间窗: From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.
To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2
次要结局
- Peak Plasma Concentration of ZX-101A(Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5)
- Half-life of ZX-101A(Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5)
- Phospho-AKT (p-AKT) levels in whole blood(Days 1 and 2 of Cycle 1 (each cycle is 28 days))
- Objective response rate (ORR)(Up to 2 years)
- Duration of response (DoR)(Up to 2 years)
- Area under the plasma concentration of ZX-101A(Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5)
- Progression free survival (PFS)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)