An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 入组人数
- 84
- 试验地点
- 45
- 主要终点
- Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL
研究概览
简要总结
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)
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
- •Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant
- •Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment
- •ECOG 0 to 2
- •Adequate hematologic, hepatic, and renal functions.
排除标准
- •Prior treatment with any MDM2 inhibitor
- •Prior treatment with any BTK inhibitor
研究组 & 干预措施
Cohort 1 (R/R DLBCL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: KRT-232 (Drug)
Cohort 1 (R/R DLBCL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: acalabrutinib (Drug)
Cohort 2 (R/R CLL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: KRT-232 (Drug)
Cohort 2 (R/R CLL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
干预措施: acalabrutinib (Drug)
结局指标
主要结局
Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL
时间窗: 56 Days
Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
时间窗: 1 Year
Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
时间窗: 1 Year
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
次要结局
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile(Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2)
- Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.(2 Years)
- Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects(2 Years)