A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study to Determine the Safety and Efficacy of BGB-11417as Monotherapy, in Combination With Dexamethasone, Dexamethasone/Carfilzomib, Dexamethasone/Daratumumab, and Dexamethasone/Pomalidomide in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14)
概览
- 阶段
- 1 期
- 干预措施
- Sonrotoclax
- 疾病 / 适应症
- 未指定
- 发起方
- BeOne Medicines
- 入组人数
- 246
- 试验地点
- 139
- 主要终点
- Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 10天前
概览
简要总结
The purpose of this study is to assess the safety, tolerability, and efficacy of sonrotoclax as monotherapy and in various combinations in patients with relapsed/refractory (R/R) multiple myeloma (MM) and chromosomal translocation t(11;14).
The study investigates sonrotoclax alone and in combination with dexamethasone and other agents, including carfilzomib, daratumumab, and pomalidomide.
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.
研究者
入排标准
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)
- •Measurable disease defined as:
- •i. M-spike ≥ 500mg/dL, or ii. Urine protein M-spike of ≥ 200 mg/day, or iii. Serum free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio
- •Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy.
- •i. Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM.
- •ii. Refractory MM is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy or progresses within 60 days of last therapy.
- •In Part 1 and Part 2 Cohorts 1 and 2 participants should have relapsed or progressive disease and have had ≥ 3 prior lines of therapy including a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody, and no more available approved therapies.
- •Participants in Part 2 Cohorts 3, 4, and 5 should have relapsed or progressive disease and have had ≥ 1 prior line of therapy. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory by the investigator.
- •Participants in Part 2 Cohorts 6 and 7 should have relapsed or progressive disease and have had 1 to 3 prior lines of therapy and previously treated with a proteasome inhibitor and an IMiD
排除标准
- •Participant has any of the following conditions:
- •Non secretory MM (Serum free light chains \< 10 mg/dL)
- •Solitary plasmacytoma
- •Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or \> 2.0 x 109/L circulating plasma cells by standard differential)
- •Waldenström macroglobulinemia (WM)
- •Amyloidosis.
- •Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome
- •Chronic respiratory disease that requires continuous oxygen
- •Significant cardiovascular disease, including but not limited to:
- •Myocardial infarction ≤ 6 months before screening
研究组 & 干预措施
Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.
干预措施: Sonrotoclax
Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.
干预措施: Carfilzomib
Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.
干预措施: Dexamethasone
Part 2 Cohort Expansion
There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab
干预措施: Dexamethasone
Part 2 Cohort Expansion
There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab
干预措施: Carfilzomib
Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.
干预措施: Daratumumab
Part 2 Cohort Expansion
There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab
干预措施: Sonrotoclax
Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.
干预措施: Pomalidomide
结局指标
主要结局
Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)
时间窗: Up to 28 days
DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.
Part 1 And 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation and Adverse Events of Special Interest (AESIs).
时间窗: Up to 30 days after last dose of study drug
Part 2: Overall response rate (ORR) as Assessed by Investigator
时间窗: Approximately 4 years
Defined as the percentage of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) criteria
Part 2: Very Good Partial Response (VGPR) or Better Response Rate as Assessed by Investigator
时间窗: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]
Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)
Part 2: Complete Response (CR) or Stringent Complete Response (sCR) as Assessed by Investigator
时间窗: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])
defined as the percentage of participants with a documented CR or sCR
次要结局
- Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax(Cycle 1 (each cycle is up to 28 days))
- Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax(Cycle 1 (each cycle is up to 28 days))
- Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax(Cycle 1 (each cycle is up to 28 days))
- Part 1: At Steady-state: AUC last, ss(Cycle 2 (each cycle is up to 28 days))
- Part 1: At Steady-state: Cmax, ss(Cycle 2 (each cycle is up to 28 days))
- Part 1: At Steady-state: trough plasma concentration (Ctrough) ss(Cycle 2 (each cycle is up to 28 days))
- Part 1: At Steady-state: time to reach Cmax (tmax,ss)(Cycle 2 (each cycle is up to 28 days))
- Part 2: Time to response (TTR) as Assessed by Investigator(Approximately 4 years)
- Part 2: Duration of response (DOR) as Assessed by Investigator(Approximately 4 years)
- Part 2: Progression-free survival (PFS) as Assessed by Investigator(Approximately 4 years)
- Part 2: Overall survival (OS) as Assessed by Investigator(Approximately 4 years)