A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl‑2 Inhibitor BGB‑11417 in Patients With Myeloid Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 53
- 试验地点
- 12
- 主要终点
- Part 1 (dose regimen finding) and Part 2 (safety expansion) • Safety and tolerability of BGB-11417 in combination with azacitidine as assessed by dose-limiting toxicities (DLTs)and the incidence, timing, and severity of treatment-emergent adverse events (TEAEs), according to NCI-CTCAE v5.0.
研究概览
简要总结
Part 1 (dose regimen finding) and Part 2 (safety expansion) • To determine the safety and tolerability of BGB-11417 in combination with azacitidine in patients with myeloid malignancies • To select the dose regimens of BGB-11417 in combination with azacitidine to be evaluated in Part 2 (in Part 1 only) • To determine the recommended Phase 2 dose (RP2D) of BGB-11417 in combination with azacitidine to be evaluated in Part 3
Part 3 (efficacy expansion) • To evaluate the antileukemic activity of BGB-11417 in combination with azacitidine as measured by response rates • To evaluate the effect of posaconazole on the pharmacokinetics of BGB-11417 when coadministered in a drug-drug interaction (DDI) cohort (Note: the DDI evaluation with posaconazole will not be conducted in Europe)
For monotherapy: to determine the safety and tolerability of BGB-11417 monotherapy in patients with R/R AML, MDS and MDS/MPN
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Confirmed diagnosis of one of the following by 2016 World Health Organization criteria: • acute myeloid leukemia (AML), nonacute promyelocytic leukemia; • myelodysplastic syndrome (MDS); or • myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ function defined as: • Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort) • Adequate liver function
- •Life expectancy of > 12 weeks.
- •Ability to comply with the requirements of the study.
- •Note: other protocol-defined inclusion criteria may apply.
排除标准
- •A diagnosis of acute promyelocytic leukemia.
- •Prior malignancy within the past 2 years, except for curatively treated localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
- •Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
- •Prior therapy with a B-cell lymphoma-2 inhibitor or azacitidine except for participants who meet HMA-failure critera.
- •Known central nervous system involvement by leukemia.
- •Note: other protocol-defined exclusion criteria may apply.
结局指标
主要结局
Part 1 (dose regimen finding) and Part 2 (safety expansion) • Safety and tolerability of BGB-11417 in combination with azacitidine as assessed by dose-limiting toxicities (DLTs)and the incidence, timing, and severity of treatment-emergent adverse events (TEAEs), according to NCI-CTCAE v5.0.
Part 1 (dose regimen finding) and Part 2 (safety expansion) • Safety and tolerability of BGB-11417 in combination with azacitidine as assessed by dose-limiting toxicities (DLTs)and the incidence, timing, and severity of treatment-emergent adverse events (TEAEs), according to NCI-CTCAE v5.0.
Part 3 (efficacy expansion) • For AML: - complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate; - In the DDI cohort: PK endpoints of BGB-11417, including but not limited to area under the curve (AUC) and maximum plasma concentration (Cmax), derived from the plasma concentration-time profiles
Part 3 (efficacy expansion) • For AML: - complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate; - In the DDI cohort: PK endpoints of BGB-11417, including but not limited to area under the curve (AUC) and maximum plasma concentration (Cmax), derived from the plasma concentration-time profiles
• For MDS: modified overall response (mOR) rate, including CR, marrow complete remission (mCR), and partial remission (PR).
• For MDS: modified overall response (mOR) rate, including CR, marrow complete remission (mCR), and partial remission (PR).
次要结局
- Part 1 (dose regimen finding) and Part 2 (safety expansion) For AML: • CR + morphologic complete remission with partial hematologic recovery (CRh) rate. For MDS: • Modified overall response (mOR) rate. mOR is defined as achieving a CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study per modified IWG 2006 criteria for MDS/MPN (Cheson et al 2006)
- Secondary pharmacokinetic (PK) endpoints for both AML and MDS: • Derived PK parameters, including: − For azacitidine: maximum observed plasma concentration (Cmax), area under plasma concentration-time curve (AUC0-t, AUC0-∞), half-life (t1/2), apparent total clearance of drug from plasma (CL/F), and apparent volume of distribution (Vz/F) as appropriate; − For BGB-11417: AUClast,ss, Cmax,ss, steady-state trough plasma concentration (Ctrough,ss) and tmax,ss.
- Part 3 (efficacy expansion) For AML: • CR rate; • CR + CR with incomplete hematologic recovery (CRi) rate; • ORR (CR + CRi + PR + morphologic leukemia-free state [MLFS]); • Duration of response of CR, CR + CRi, OR and CR + CRh; • Time to response (TTR) of CR, CR + CRi, OR and CR + CRh; • Event-free survival (EFS); • Overall survival (OS). • Transfusion independence (for at least consecutive 56-day postbaseline)
- Part 3 (efficacy expansion) For MDS: • CR rate; • Hematological improvement – erythroid (HI-E), as per IWG 2018 criteria; • Hematological improvement – platelet (HI-P), as per IWG 2018 criteria; • Hematological improvement – neutrophil (HI-N), as per IWG 2018 criteria; • Transfusion independence (for at least consecutive 56-day post-baseline); • EFS; • OS.
- Safety endpoints for both AML and MDS: • Safety and tolerability of BGB-11417 in combination with azacitidine or posaconazole as assessed by the incidence, timing, and severity of TEAEs, according to NCI-CTCAE v5.0.
研究者
BeiGene Clinical Support
Scientific
Beigene Ltd.