Phase I/II, First in Human, Dose Escalation Trial of TL 895 Monotherapy in Subjects With Relapsed/Refractory B Cell Malignancies and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Subjects and Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 130
- 试验地点
- 17
- 主要终点
- Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1
研究概览
简要总结
The purpose of this research study is to determine the safety and tolerability of TL-895. There are 2 parts of this study. Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory (R/R) B cell malignancies who failed at least 1 but no more than 3 prior therapies. Part 1 of this study is no longer enrolling participants.
Arms 1 & 2 of Part 2 of this study will test different doses of TL-895 in participants with R/R CLL or SLL who have failed at least 1 prior therapy. Arms 1 & 2 of Part 2 of this study is randomized (like the flip of a coin) to receive a specific treatment dose. If someone participates in arms 1 or 2 of Part 2, the dose they receive will be either 100mg twice a day or 150mg twice a day.
Arms 3 and 4 of Part 2 of this study will test the 150mg and 100mg BID dose of TL-895, respectively in treatment naïve participants with CLL/SLL.
Arms 5 and 6 of Part 2 will test 150mg TL-895 BID in combination with 240 mg navtemadlin QD in participants with relapsed/refractory and treatment naïve without 17p(del). Arm 7 will test 150mg TL-895 in combination with 240 mg navtemadlin QD in participants with relapsed/refractory CLL/SLL with 17p(del).
Every participant in this study will receive TL-895.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
TL-895 80/160 mg QD in R/R Participants
Participants received TL-895 80 mg powder in capsule (PiC) orally once daily (OD) for 3 days followed by TL-895 160 mg OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 300 mg QD in R/R Participants
Participants received TL-895 300 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 600 mg QD in R/R Participants
Participants received TL-895 600 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 300 mg BID in R/R Participants
Participants received TL-895 300 mg PiC orally twice daily (BID) in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 900 mg QD in R/R Participants
Participants received TL-895 900 mg PiC orally QD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 100 mg BID in R/R Participants
Participants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID in R/R Participants
Participants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID in Treatment Naïve Participants
Participants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 100 mg BID in Treatment Naïve Participants
Participants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: Navtemadlin (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: Navtemadlin (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: TL-895 (Drug)
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)
Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
干预措施: Navtemadlin (Drug)
结局指标
主要结局
Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1
时间窗: Baseline up to the end of cycle 1 (28 days)
DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.
Part 2 (Dose Expansion): Overall Response Rate (ORR)
时间窗: Baseline up to end of study (2 years after last patient enrolled)
The proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria (2), as assessed by investigators
次要结局
- Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS)(Baseline up to 6 months on treatment)
- Part 2 (Dose Expansion): Overall CR/CRi rate(Baseline up to end of study (2 years after last patient enrolled))
- Part 2: Duration of Clinical Response (DOR)(Baseline up to end of study (2 years after last patient enrolled))
- Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)(Baseline up to end of study (2 years after last patient enrolled))
- Part 2: Assessment of Safety and Tolerability via Clinical Measurements(Baseline up to end of study (2 years after last patient enrolled))