A Multi-Center, Open-Label Phase II Study of IBI3003 in Combination With Anti-CD38 Monoclonal Antibody in Participants With Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- TEAE(Treatment emergent adverse event)
研究概览
简要总结
This is an open-label, multi-center phase II study of IBI3003 in combination with anti-CD38 monoclonal antibody in adult subjects with multiple myeloma. This study includes a safety run-in period and 2 cohorts (Cohorts 1 and 2).In the safety run-in period, subjects with measurable relapsed or refractory multiple myeloma who had previously received at least 1 line of systemic anti-myeloma therapy and had a history of dual drug exposure (at least one proteasome inhibitor and one immunomodulatory agent) were enrolled, mainly to evaluate the safety and tolerability of IBI3003 in combination with anti-CD38 monoclonal antibody and to determine the recommended phase 2 dose of IBI3003 in combination with anti-CD38 monoclonal antibody.Cohort 1 mainly enrolls newly diagnosed MM(Multiple myeloma)patients who are ineligible for or refusing ASCT(Autologous Stem Cell Transplantation), and Cohort 2 enrolls newly diagnosed MM patients who are eligible for and willing to undergo ASCT. The 24-week MRD negative rate of IBI3003 in combination with anti-CD38 monoclonal antibody in the participant population is mainly evaluated.
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
- •1. Aged at least 18 years old;
- •2. Initial diagnosis of multiple myeloma documented according to International Myeloma Working Group (IMWG) diagnostic criteria.Multiple myeloma is defined as clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma, and any one or more of the following myeloma-defining events: • Evidence of end-organ damage attributable to the underlying plasma cell proliferative disorder, including the following: Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) above the upper limit of normal or corrected serum calcium > 2.75 mmol/L (> 11 mg/dL); renal insufficiency: creatinine clearance < 40 mL/min or serum creatinine > 177 μmol/L (> 2 mg/dL); anemia: hemoglobin value > 2 g/dL below the lower limit of normal or hemoglobin value < 10 g/dL; bone lesions: one or more osteolytic lesions on skeletal radiographs, computed tomography (CT), or positron emission tomography (PET)-CT.
- •Any one or more of the following biomarkers of malignancy: Clonal bone marrow plasma cell percentage ≥ 60%; involved-to-uninvolved serum free light chain ratio ≥ 100 [involved serum free light chain (FLC) level must be ≥ 100 mg/L]; > 1 focal lesion (at least 5 mm in size) on magnetic resonance imaging (MRI) examination.
- •3.Safety run-in stage: Relapsed or refractory measurable multiple myeloma who have previously received ≥ 1 line of anti-myeloma therapy (including treatment with at least one proteasome inhibitor and one immunomodulatory drug), and the participant must be relapsed or refractory to the most recent treatment.Participants previously exposed to anti-CD38 monoclonal antibodies may also be enrolled (a 90-day washout period is required).
- •Note: Refractory to antimyeloma therapy requires failure to achieve minimal response (receipt of at least 2 complete cycles) or progression during treatment (no requirement for number of treatment cycles), or progression within 60 days of last treatment.
- •Cohort 1: Participants with newly diagnosed multiple myeloma who are ineligible for or refusing ASCT.
- •Cohort 2: Participants with newly diagnosed multiple myeloma who are eligible for and interested in ASCT.
- •4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •5. At least one of the following measurable disease indicators: • Serum M protein >= 5 g/L (for IgA and IgD subtypes, quantitative immunoglobulin measurement can be used to replace M protein); • Urine M protein >= 200mg/24h; • FLC test: involved FLC level >= 100 mg/L and abnormal FLC ratio (< 0.26 or > 1.65).
排除标准
- •1. All subjects have previously received any treatment targeting BCMA and any treatment targeting GPRC5D.Participants who have received either a BCMA-directed or GPRC5D-directed therapy are allowed.
- •2. Known active central nervous system (Central Nervous System, CNS) involvement or clinical symptoms of meningeal involvement of multiple myeloma.
- •3. Has amyloidosis, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, solitary plasmacytoma, or smoldering (asymptomatic) multiple myeloma as defined by IMWG criteria.
- •4. Patients with spinal cord compression resulting in limited self-care at present or within 6 months before signing the informed consent form, or expected to result in such restrictions during study participation.
- •5. History of primary immunodeficiency.
- •6. Other malignant tumors (except for cured basal cell or squamous cell skin cancer, superficial bladder cancer, prostatic intraepithelial neoplasia, cervical carcinoma in situ, or other non-invasive or indolent malignant tumors) at the time of enrollment or within 3 years prior to enrollment.
- •7. Received allogeneic hematopoietic stem cell transplantation within 6 months prior to the first dose of study drug, or received autologous stem cell transplantation within 3 months prior to the first dose of study drug.
- •8. History of organ transplantation.
- •9. Active graft-versus-host disease.
研究组 & 干预措施
treatment group
干预措施: IBI3003 (Biological)
Standard-of-care control group
干预措施: Daratumumab (Drug)
Standard-of-care control group
干预措施: Lenalidomide (Drug)
treatment group
干预措施: Daratumumab (Drug)
Standard-of-care control group
干预措施: Dexamethasone (Drug)
结局指标
主要结局
TEAE(Treatment emergent adverse event)
时间窗: 30Days
Adverse events will be assessed by investigator(s) according to NCI-CTCAE V5.0
MRD（ Minimal Residue Disease) negativity rate at 24 weeks
时间窗: 24weeks
Defined as the percentage of participants who achieved MRD-negative status at or below the threshold of 10-5 at any time after the first treatment.
AE(Adverse event)
时间窗: 30Days
Adverse events will be assessed by investigator(s) according to NCI-CTCAE V5.0
SAE（Serious Adverse Event）
时间窗: 30Days
Adverse events will be assessed by investigator(s) according to NCI-CTCAE V5.0
AESI( Adverse event of special interest)
时间窗: 30Days
Adverse events will be assessed by investigator(s) according to NCI-CTCAE V5.0
次要结局
- Progression-Free Survival (PFS)(3years)
- ORR(objective response rate)(3years)
- AE(Adverse event)(12Months)
- TEAE(Treatment emergent adverse event)(12Months)
- SAEs(serious adverse events)(12Months)
- AESI( Adverse event of special interest)(12Months)