A Phase 1-2, Open-Label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects With Relapsed/Refractory Peripheral T-cell Lymphoma
概览
- 阶段
- 1 期
- 干预措施
- Tolinapant
- 疾病 / 适应症
- Relapsed/Refractory Peripheral T-cell Lymphoma
- 发起方
- Taiho Oncology, Inc.
- 入组人数
- 33
- 试验地点
- 46
- 主要终点
- Phase 2: Antitumor Activity Assessed by Overall Response Rate (ORR) Based on 2014 Lugano Classification Using Computerized Tomography (CT) Imaging as the Primary Modality
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
The primary purpose of the study is to assess safety, and to identify the recommended phase 2 dose (RP2D) of tolinapant in combination with oral decitabine/cedazuridine in Phase 1 and to assess preliminary efficacy as determined by overall response rate (ORR) in Phase 2.
As no safe and tolerable dosing for the combination of tolinapant and decitabine/cedazuridine was identified based on protocol defined criteria, Sponsor decided to halt recruitment and to not conduct Phase 2 of the study.
研究者
入排标准
入选标准
- •Participants with expected life expectancy of \>12 weeks.
- •Participants must have histologically confirmed R/R PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study:
- •Extranodal natural killer (NK)/T-cell lymphoma nasal type.
- •Enteropathy-associated T-cell lymphoma.
- •Monomorphic epitheliotropic intestinal T-cell lymphoma.
- •Hepatosplenic T-cell lymphoma.
- •Subcutaneous panniculitis-like T-cell lymphoma.
- •Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
- •Angioimmunoblastic T-cell lymphoma.
- •Follicular peripheral T-cell lymphoma.
排除标准
- •Prior treatment with tolinapant or any hypomethylating agent.
- •Hypersensitivity to tolinapant or oral decitabine/cedazuridine, excipients of the drug product, or other components of the study treatment regimen.
- •Poor medical risk because of systemic diseases (e.g., uncontrolled infections) in addition to the qualifying disease under study.
- •Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participant safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of tolinapant.
- •A history of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
- •Abnormal left ventricular ejection fraction.
- •Congestive cardiac failure of Grade ≥
- •Unstable cardiac disease.
- •History or presence of complete left bundle branch block, third-degree heart block, cardiac pacemaker, or clinically significant arrhythmia.
- •History of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
研究组 & 干预措施
Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine
Tolinapant, orally, once daily (QD) on Days 1 to 7 and 15 to 21 of each 28-day cycle in combination with oral decitabine/cedazuridine fixed-dose combination (FDC) tablet, QD on days determined by the Lead-in Phase during each 28-day cycle. The starting dose of tolinapant will be escalated stepwise in successive cohorts until the RP2D is determined. Based on RP2D and results determined from Phase 1 participants would receive tolinapant at the identified RP2D in combination with decitabine/cedazuridine, FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle in Phase 2.
干预措施: Tolinapant
Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine
Tolinapant, orally, once daily (QD) on Days 1 to 7 and 15 to 21 of each 28-day cycle in combination with oral decitabine/cedazuridine fixed-dose combination (FDC) tablet, QD on days determined by the Lead-in Phase during each 28-day cycle. The starting dose of tolinapant will be escalated stepwise in successive cohorts until the RP2D is determined. Based on RP2D and results determined from Phase 1 participants would receive tolinapant at the identified RP2D in combination with decitabine/cedazuridine, FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle in Phase 2.
干预措施: Decitabine + Cedazuridine
Phase 1: Oral Decitabine/Cedazuridine
Decitabine/cedazuridine FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle.
干预措施: Decitabine + Cedazuridine
结局指标
主要结局
Phase 2: Antitumor Activity Assessed by Overall Response Rate (ORR) Based on 2014 Lugano Classification Using Computerized Tomography (CT) Imaging as the Primary Modality
时间窗: Up to 54 months
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs)
时间窗: Up to 54 months
This will be evaluated by looking at the number of participants with treatment-related adverse events, serious adverse events (SAEs), and dose-limiting toxicities (DLTs), which are medical problems severe enough to stop study doctors from increasing a treatment dose.
次要结局
- Phase 2: Percentage of Participants With Complete Response (CR) Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Ph 1 & 2: AUC: Area Under the Plasma Concentration-Time Curve(Up to 50 months)
- Phase 2: Percentage of Participants With Partial Response (PR) Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Phase 2: Percentage of Participants With Anti-Tumor Activity Based on PTCL Subtypes Anti-tumor activity in terms of ORR, DOR, DCR, CR, and PR will be evaluated based on PTCL subtypes (using both pathology and molecular markers).(Up to 54 months)
- Ph 1 & 2: Tmax: Time to Maximum Observed Plasma Concentration(Up to 50 months)
- Phase 2: Overall Survival (OS) Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Ph 1 & 2: t½: Apparent Elimination Half-Life(Up to 50 months)
- Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration(Up to 50 months)
- Phase 2: Duration of response (DOR) Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Phase 2: Disease Control Rate (DCR) Assessed as Percentage of Participants With Disease Control Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Phase 1: Number of Participants With TEAEs, SAEs and DLTs in the Oral Decitabine/Cedazuridine Arm(Up to 54 months)
- Ph 1 & 2: Cmin: Minimum Observed Plasma Concentration at Steady State(Up to 50 months)
- Phase 2: Progression-Free Survival (PFS) Based on the Lugano Classification Using CT Imaging as the Primary Modality(Up to 54 months)
- Phase 2: Percentage of Participants With Anti-Tumor Activity Based on Assessment Using 2014 Lugano Classification With Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)(Up to 54 months)
- Phase 2: Percentage of Participants With DOR, CR, PR, PFS, DCR,and OS Based on the Lugano Classification Using CT Along With PET Imaging Assessments(Up to 54 months)