A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Participants With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 29
- 主要终点
- Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
The purpose of this study is to evaluate the safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared with daratumumab SC alone, in participants with relapsed or refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Prior diagnosis of multiple myeloma according to IMWG diagnostic criteria.
- •Measurable disease at screening.
- •Has received at least 3 but not more than 5 prior lines of multiple myeloma treatment, including proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapies.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Willing to avoid pregnancy or fathering children.
- •Willing to provide fresh and archival bone marrow aspiration and biopsy tissue.
排除标准
- •Receipt of any of the following treatment within the indicated interval before the first administration of study drug:
- •Anti-myeloma treatment within 2 weeks or 5 half-lives (whichever is longer).
- •Investigational drug (including investigational vaccines) or invasive investigational medical device within 4 weeks.
- •Autologous stem cell transplant within 12 weeks, or allogeneic stem cell transplant at any time.
- •Plasmapheresis within 4 weeks.
- •Radiation therapy within 2 weeks.
- •Major surgery within 2 weeks, or inadequate recovery from an earlier surgery, or surgery planned during the time the participant is expected to participate in the study or within 2 weeks after the last dose of study treatment.
- •Toxicity ≥ Grade 2 from previous anti-myeloma therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
- •Known additional malignancy (other than multiple myeloma) that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
- •Laboratory values at screening outside the protocol-defined range.
- •Significant concurrent, uncontrolled medical condition including but not limited to known chronic obstructive pulmonary disease (COPD), persistent asthma, or history of asthma within the past 2 years; chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment; acute diffuse infiltrative pulmonary disease; clinically significant or uncontrolled cardiac disease.
- •Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or amyloidosis.
研究组 & 干预措施
INCB001158 + daratumumab SC
INCB001158 + daratumumab
干预措施: INCB001158 (Drug)
INCB001158 + daratumumab SC
INCB001158 + daratumumab
干预措施: Daratumumab SC (Biological)
Daratumumab monotherapy and crossover to INC001158+ daratumumab SC
Daratumumab will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.
干预措施: Daratumumab SC (Biological)
INCB001158 monotherapy and crossover to INC001158+ daratumumab SC
INCB001158 will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.
干预措施: INCB001158 (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to 454 days
A TEAE was defined as an adverse event (AE) that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria
时间窗: up to Day 386
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) \<100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to \<200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
次要结局
- Phase 2: Number of Participants With Any TEAE(up to 420 days)
- Overall Survival(up to 923 days (approximately 2.5 years))
- Phase 2: MRD, Defined as the Percentage of MRD-negative Participants(up to approximately 2 years)
- Phase 1: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First(up to Day 395)
- Phase 2: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First(up to Day 386)
- Progression-free Survival (PFS), Defined as the Duration From the Date of the First Dose of Study Drug Until Either Progressive Disease, as Per IMWG Criteria, or Death, Whichever Occurred First(up to approximately 2 years)
- Phase 1: Time to Response, Defined as the Time From the First Dose of Study Drug to the First Documented Response of PR or Better (CR, VGPR, or PR), as Per IMWG Criteria(up to Day 395)
- Phase 2: Time to Response, Defined as the Time From the First Dose of Study Drug to the First Documented Response of PR or Better (CR, VGPR, or PR), as Per IMWG Criteria(up to Day 386)
- Phase 1: Minimal Residual Disease (MRD), Defined as the Percentage of MRD-negative Participants(up to approximately 2 years)
- Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria(up to Day 395)