A Modular Phase I/II, Open-label, Dose Escalation and Expansion, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Patients With Advanced Non-Hodgkin Lymphoma.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events (AE)
研究概览
简要总结
This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL
详细描述
This is a modular Phase I/II, open-label, dose escalation and expansion, multicentre Study. The study consists of individual modules, each evaluating the safety and tolerability of AZD0466 as monotherapy or with a specific combination treatment. The initial components are the core protocol, which contains information applicable to all modules, and Module 1.
Module 1 will evaluate the safety, tolerability, PK, and preliminary efficacy of AZD0466 monotherapy and will include 2 parts. Part A dose escalation and Part B dose expansion cohorts. Part A will enrol patients with advanced B-NHL and once the RP2D has been determined, Part B may open to further explore the preliminary anticancer efficacy of AZD0466 monotherapy in patients with selected lymphoid malignancies.
Part A: Phase 1 dose setting to assess the safety and tolerability and determine dose(s) and schedule(s) to be evaluated in Part B.
Part B: Phase 1b/2a dose expansion to assess the efficacy of AZD0466 in 3 select patient populations: relapsed/refractory (R/R) mantle cell lymphoma (MCL) (Cohort B1), R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) (Cohort B2), and R/R diffuse large B-cell lymphoma (DLBCL) (Cohort B3).
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 130 Years（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
Part A (Dose Escalation): Dose Level (DL)-1
Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part A (Dose Escalation): DL1
Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part A (Dose Escalation): DL2
Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part A (Dose Escalation): DL3
Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part A (Dose Escalation): DL4
Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part B (Dose Expansion): Cohort B1 (R/R MCL)
Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part B (Dose Expansion): Cohort B2 (R/R FL or MZL)
Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
Part B (Dose Expansion): Cohort B3 (R/R DLBCL)
Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
干预措施: AZD0466 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AE)
时间窗: Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: Day 1 to end of Cycle 1 (28 days treatment cycle)
The DLT of AZD0466 in participants with R/R B-NHL was evaluated.
次要结局
- Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320(Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22))
- Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320(Cycle 1 Day 8)
- Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Concentration Prior to Dosing (Ctrough) of AZD4320(Cycle 2 Day 1)
- Part A:Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Analyte Concentration Divided by the Dose Administered (Dose Normalised AUClast) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)
- Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (Dose Normalised AUC0-72) of AZD4320(Cycle 1 Day 8)
- Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320(Cycle 1 Day 8, Cycle 2 Day 1)