A Phase 1/1b, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of KQB198 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 122
- 试验地点
- 29
- 主要终点
- Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1)
研究概览
简要总结
The goal of this clinical trial is to learn if KQB198 works to treat advanced hematologic malignancies in adults. It will also learn about the safety of KQB198. The main questions it aims to answer are:
- What is the safe dose of KQB198 by itself or in combination with other anti-cancer drugs?
- Does KQB198 alone or in combination with other anti-cancer drugs decrease the size of the tumor?
- What happens to KQB198 in the body?
Participants will:
- Take KQB198 daily, alone or in combination with another anti-cancer drug
- Visit the clinic about 8 times in the first 8 weeks, and then once every 4 weeks after that
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
- •Adequate organ function
- •Part 1 and Part 2, Cohort B Participants Only:
- •Ph+ CML in chronic phase who have been previously treated with at least 2 different tyrosine kinase inhibitors (TKIs) and are relapsed from or intolerant to those TKIs and ineligible for alternative therapeutic options likely to produce clinical benefit as determined by the investigator.
- •Part 2, Cohort A Participants Only:
- •Participants with Ph+ CML in chronic phase who are on dasatinib prior to study entry and have a warning or failure to dasatinib as determined by the investigator per ELN 2020 guidelines
排除标准
- •CML in accelerated or blast phase
- •Prior therapy with a similar mechanism of action to KQB198
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- •History of interstitial lung disease
- •Cardiac abnormalities
研究组 & 干预措施
Monotherapy Dose Expansion - RP2D -1
干预措施: KQB198 (Drug)
Combo Therapy Dose Expansion - RP2D
干预措施: Dasatinib (Drug)
Combo Therapy Dose Expansion - RP2D-1
干预措施: KQB198 (Drug)
Combo Therapy Dose Expansion - RP2D-1
干预措施: Dasatinib (Drug)
Monotherapy Dose Expansion - RP2D
干预措施: KQB198 (Drug)
Monotherapy Dose Escalation
干预措施: KQB198 (Drug)
Combo Therapy Dose Escalation
干预措施: KQB198 (Drug)
Combo Therapy Dose Escalation
干预措施: Dasatinib (Drug)
Combo Therapy Dose Expansion - RP2D
干预措施: KQB198 (Drug)
结局指标
主要结局
Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 1)
时间窗: 28 Days
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, SAEs, and DLTs, from first dose of study treatment to 28 days after last dose of study treatment.
Recommended Phase 2 Dose (RP2D) (Part 1)
时间窗: Up to 30 months
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the RP2D.
Efficacy of study treatment and optimal biologic dose, as measured by molecular response (MR) per European Leukemia Network (ELN) 2020 Guidelines (Part 2).
时间窗: Up to 6 Months
Molecular response is the percentage of BCR-ABL fusion protein found in blood. Calculation of molecular response in Part 2 Cohort A will be the proportion of subjects that experience molecular response 4 (MR4) during the time period from 1st dose of study treatment until 6 months of study treatment. Calculation of molecular response in part 2 cohort B will be the proportion of subjects that experience molecular response 3 (MR3) during the time period from 1st dose of study treatment until 6 months of study treatment.
次要结局
- Efficacy of Study Treatment(Up to 30 months)
- Number of patients who experience treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities (Part 2)(28 Days After Last Dose)
- Concentration-Time Curve (AUC)(Up to 30 months)
- Maximum Plasma Concentration (Cmax)(Up to 30 months)
- Time to Maximum Plasma Concentration (tmax)(Up to 30 months)