A Phase 1/2a, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD 38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MorphoSys AG
- 入组人数
- 91
- 试验地点
- 10
- 主要终点
- Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
研究概览
简要总结
This is an open-label, multicentre, dose escalation study to characterize the safety and preliminary efficacy of the human anti-CD38 antibody MOR03087 (MOR202), in adult subjects with relapsed/refractory multiple myeloma, as monotherapy and in adult subjects with relapsed/refractory multiple myeloma in combination with standard therapy.
详细描述
The study enrolled patients aged 18 years or older with relapsed or refractory multiple myeloma and Karnofsky performance status of 60% or higher. Patients were assigned to the different treatment regimens with MOR202 ranging between 0·01 mg/kg and 16 mg/kg in a 3 + 3 design. Dose-escalation and expansion was done either with MOR202 intravenous infusions alone (MOR202 q2w [twice a week] and q1w [weekly] groups) or in combination with dexamethasone (MOR202 with dexamethasone group), with dexamethasone plus pomalidomide (MOR202 with dexamethasone plus pomalidomide group) or plus lenalidomide (MOR202 with dexamethasone plus lenalidomide group). Primary endpoints were safety, MOR202 maximum tolerated dose (or recommended dose) and regimen, and immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Male or female subjects 18 years and older
- •Relapsed or refractory multiple myeloma defined as:
- •Parts A, B and C:
- •(i) Failure of at least 2 previous therapies which must have included an immunomodulatory agent and a proteasome inhibitor (either together or part of different therapies) (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
- •(i) At least 2 previous therapies including lenalidomide and a proteasome inhibitor (ii) All subjects must have documented progression during or within 60 days after their last prior therapy for multiple myeloma
- •(i) Received at least one previous therapy (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
- •Presence of serum M-protein ≥ 0.5 g per 100 mL (≥ 5 g/L) and / or urine M-protein ≥ 200 mg per 24-hour period
- •Absolute neutrophil count (ANC) ≥ 1,000 / mm3
- •Haemoglobin ≥ 8 g/dL
- •Ability to comply with all study related procedures, medication use and evaluations
排除标准
- •Primary refractory multiple myeloma
- •History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity grade 3 or higher
- •Treatment with systemic investigational agent within 28 days prior to first study treatment
- •Solitary plasmacytoma or plasma cell leukaemia
- •Previous allogenic stem cell transplant (SCT)
- •Prior therapy with other monoclonal antibodies targeting the CD38 antigen or prior therapy with other IgG monoclonal antibodies within 3 months prior to first study treatment, or IgM monoclonal antibodies within 1 month prior to first study treatment
- •Active systemic infection
- •Systemic disease preventing study treatment
- •Multiple myeloma with central nervous system (CNS) involvement
- •Previous treatment with cytotoxic chemotherapy or large field radiotherapy or other myeloma specific therapy within 28 days prior to first study treatment (radiation to a single site as concurrent therapy is allowed)
- •Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] classes III, IV)
研究组 & 干预措施
Phase 1 dose escalation
Part A: MOR03087 dose escalation; biweekly treatment
Part B: MOR03087 dose escalation; weekly treatment
Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone
Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone
Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone
For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
干预措施: MOR03087 phase 1 dose escalation (Drug)
Phase 1 dose escalation
Part A: MOR03087 dose escalation; biweekly treatment
Part B: MOR03087 dose escalation; weekly treatment
Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone
Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone
Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone
For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
干预措施: Dexamethasone (Drug)
Phase 1 dose escalation
Part A: MOR03087 dose escalation; biweekly treatment
Part B: MOR03087 dose escalation; weekly treatment
Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone
Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone
Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone
For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
干预措施: Pomalidomide (Drug)
Phase 1 dose escalation
Part A: MOR03087 dose escalation; biweekly treatment
Part B: MOR03087 dose escalation; weekly treatment
Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone
Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone
Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone
For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
干预措施: Lenalidomide (Drug)
Phase 2a confirmatory cohorts
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.
Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.
Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.
For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
干预措施: MOR03087 (Drug)
Phase 2a confirmatory cohorts
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.
Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.
Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.
For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
干预措施: Dexamethasone (Drug)
Phase 2a confirmatory cohorts
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.
Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.
Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.
For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
干预措施: Pomalidomide (Drug)
Phase 2a confirmatory cohorts
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.
Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.
Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.
For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
时间窗: First cycle of treatment
1. as monotherapy 2. in combination with dexamethasone 3. in combination with pomalidomide + dexamethasone 4. in combination with lenalidomide + dexamethasone
Number of Participants Who Develop Anti-MOR03087 Antibodies
时间窗: during treatment period, maximum 3 years after 1st dose
Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity
次要结局
- Overall Response Rate(maximum 3 years after 1st dose)
- Time to Progression(patients were observed for up to 36 months)
- Progression-free Survival(patients were observed up to 36 months)
- Duration of Response(patients were observed up to 36 months)
- Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202(up to 7 days after last MOR202 dose)
- Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202(56 days)