A Phase 1/2, Dose Escalation Safety and Tolerability Study of AO-176 as Monotherapy and in Combination With Bortezomib and Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Phase 1: MTD / RP2D of AO-176 assessed by incidence of dose-limiting toxicities and incidence of treatment-related adverse events (TEAEs) as assessed by CTCAE v5.0
研究概览
简要总结
Open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics and initial efficacy of AO-176 as monotherapy and in combination with dexamethasone and bortezomib in adults with relapsed/refractory multiple myeloma (MM).
详细描述
An open-label, multicenter, dose escalation study to evaluate the safety, tolerability and PK/pharmacodynamics of AO-176 in adults with relapsed/refractory multiple myeloma whose disease has progressed following at least 3 prior systemic lines of treatment and must have progressed on the final line of therapy received before being considered for this study.
The study will be conducted in 2 phases; Phase 1 is an ascending-dose study of AO-176 monotherapy utilizing the classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT). Following the dose escalation portion and determination of the monotherapy recommended phase 2 dose (RP2D), an ascending dose escalation study of AO-176 and dexamethasone combined with bortezomib will be evaluated utilizing the same 3+3 dose escalation design.
Phase 2 will evaluate the clinical activity of AO-176 plus dexamethasone and bortezomib at the RP2D as determined in Phase 1 Part 2.
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
- •Confirmed diagnosis of symptomatic MM per IMWG criteria
- •Measurable disease
- •Relapsed or refractory to at least 3 prior systemic lines of therapy for MM
- •Eastern Cooperative Oncology Group (ECOG) status 0-2
- •Resolution of prior therapy-related adverse events
- •Minimum of 2 weeks since last dose of cancer therapy or radiotherapy
排除标准
- •Previous Grade 3-4 infusion or hypersensitivity reaction
- •Severe asthma or chronic obstructive pulmonary disease exacerbations requiring hospital admission or steroids
- •Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1 or CTLA-4) within 4 weeks.
- •Prior treatment with a therapeutic agent that targets the CD47 axis.
研究组 & 干预措施
AO-176 Dose Escalation Monotherapy
The dose escalation monotherapy cohorts will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
干预措施: AO-176 (Drug)
AO-176 + DEX Expansion Cohort
Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.
干预措施: AO-176 + Dex (Drug)
AO-176 + DEX + BORT Dose Escalation
Following evaluation of AO-176 + dexamethasone, dose escalation cohorts of AO-176 + dexamethasone + bortezomib will be enrolled. Each dose escalation cohort will initially recruit 3 patients in a standard 3+3 design; cohorts will be expanded in the event of a DLT. The Phase 2 portion of the study will further evaluate the RP2D of AO-176 + DEX + BORT.
干预措施: AO-176 + Dex + Bort (Drug)
结局指标
主要结局
Phase 1: MTD / RP2D of AO-176 assessed by incidence of dose-limiting toxicities and incidence of treatment-related adverse events (TEAEs) as assessed by CTCAE v5.0
时间窗: 12 months
Safety and tolerability of AO-176 when administered as monotherapy and in combination with dexamethasone or with dexamethasone plus bortezomib in adult patients with R/R MM as assessed by incidence of DLTs and TEAEs as assessed by CTCAE v5.0
Phase 2: Objective response rate (ORR) of AO-176 + DEX + BORT
时间窗: 12 months
Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on ORR using International Myeloma Working Group (IMWG) uniform response criteria
次要结局
- Phase 2: DCR of AO-176 + DEX + BORT(12 months)
- Phase 1: ORR of single agent AO-176(12 months)
- Phase 1: Disease control rate (DCR) of single agent AO-176(12 months)
- Phase 1: Progression-free survival (PFS) of single agent AO-176(12 months)
- Phase 1: Overall survival (OS) of single agent AO-176(12 months)
- Phase 2: PFS of AO-176 + DEX + BORT(12 months)
- Phase 2: OS of AO-176 + DEX + BORT(12 months)
- Phase 1: Duration of response (DOR) of single agent AO-176(12 months)
- Phase 2: DOR of AO-176 + DEX + BORT(12 months)