A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 437
- 试验地点
- 87
- 主要终点
- Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.
详细描述
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 one of the following:
- •NHL Cohorts:
- •MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment
- •FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
- •DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy)
- •Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1
- •CLL/SLL Cohorts:
- •CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. Requiring treatment as defined by history
- •MCL cohorts:
- •WHO-defined MCL i. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigator
- •WM cohorts:
- •g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014)
- •Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as:
- •CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry
- •DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study
- •WM: serum immunoglobulin (Ig) M level > 0.5 g/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Adequate organ function
- •Adequate pancreatic function indicated by:
- •Serum amylase ≤ 1.5 x upper limit of normal (ULN)
- •Serum lipase ≤ 1.5 x ULN
排除标准
- •Known current central nervous system involvement by lymphoma/leukemia
- •Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
- •Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Sonrotoclax Monotherapy Dose Finding: Part 1
Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral sonrotoclax evaluated as monotherapy.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.
干预措施: Obinutuzumab (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3
Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.
干预措施: Zanubrutinib (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile.
干预措施: Zanubrutinib (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.
干预措施: Zanubrutinib (Drug)
Sonrotoclax Monotherapy Expansion Cohorts: Part 2
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral sonrotoclax at the RP2D dose to further define the safety profile.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3
Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.
干预措施: Zanubrutinib (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.
干预措施: Sonrotoclax (Drug)
Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5
Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Serious Adverse Events (SAEs)
时间窗: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of Sonrotoclax
时间窗: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3: Maximum Tolerated Dose (MTD) of Sonrotoclax
时间窗: Up to approximately 2 months
Part 1, Part 3, Part 5: RP2D of Sonrotoclax
时间窗: Day 1 to last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
时间窗: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs
时间窗: Up to approximately 2 months
次要结局
- Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax(Predose up to 12 hours postdose)
- Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax(Predose up to 12 hours postdose)
- Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax(Predose up to 12 hours postdose)
- Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib(Predose up to 12 hours postdose)
- Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax(Predose up to 12 hours postdose)
- Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib(Predose up to 12 hours postdose)
- Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax(Predose up to 12 hours postdose)
- Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib(Predose up to 12 hours postdose)
- Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax(Predose up to 12 hours postdose)
- Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib(Predose up to 12 hours postdose)
- Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)(Predose up to 12 hours postdose)
- Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)(Predose up to 12 hours postdose)
- Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator(Up to 18 months)
- Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator(Up to 18 months)
- Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing(Up to 18 months)