A Phase 3, Randomized, Open-Label Study to Compare the Efficacy and Safety of Anitocabtagene Autoleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 452
- 试验地点
- 205
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The goal of this study (iMMagine-3) is to compare the study drug, anitocabtagene autoleucel to standard of care therapy (SOCT) in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug.
The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM.
详细描述
After completing the treatment period, all participants who will receive anitocabtagene autoleucel, will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.
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
- •Documented historical diagnosis of multiple myeloma (MM)
- •Received 1 to 3 prior lines of antimyeloma therapy, including an immunomodulatory drug (IMiD) and an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb). A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.
- •Documented evidence of progressive disease by IMWG criteria based on the investigator's determination on or within 12 months of the last dose of the last regimen
- •Measurable disease at screening per IMWG, defined as any of the following:
- •Serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
- •Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio
- •Only individuals who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
排除标准
- •Prior B-cell maturation antigen (BCMA)-targeted therapy
- •Prior T-cell engager therapy
- •Prior CAR therapy or other genetically modified T-cell therapy
- •Active or prior history of central nervous system (CNS) or meningeal involvement of MM
- •Cardiac atrial or cardiac ventricular MM involvement
- •History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
- •Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
- •Prior auto-SCT within 12 weeks before randomization
- •Prior allogeneic stem cell transplant (allo-SCT)
- •High-dose (eg, cumulative > 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization
- •Live vaccine ≤ 4 weeks before randomization
- •Contraindication to fludarabine or cyclophosphamide
- •History of allergy or hypersensitivity to any study agent or study drug components. Individuals with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.
- •Life expectancy < 12 weeks
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Anitocabtagene Autoleucel
Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.
干预措施: Cyclophosphamide (Drug)
Standard of Care Therapy (SOCT)
Participants will receive the investigator's choice of one of the following therapies:
- pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
- daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
- carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
- carfilzomib and dexamethasone (Kd) (28-day cycles)
干预措施: Daratumumab (Drug)
Anitocabtagene Autoleucel
Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.
干预措施: Anitocabtagene Autoleucel (Drug)
Anitocabtagene Autoleucel
Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.
干预措施: Fludarabine (Drug)
Standard of Care Therapy (SOCT)
Participants will receive the investigator's choice of one of the following therapies:
- pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
- daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
- carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
- carfilzomib and dexamethasone (Kd) (28-day cycles)
干预措施: Dexamethasone (Drug)
Standard of Care Therapy (SOCT)
Participants will receive the investigator's choice of one of the following therapies:
- pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
- daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
- carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
- carfilzomib and dexamethasone (Kd) (28-day cycles)
干预措施: Pomalidomide (Drug)
Standard of Care Therapy (SOCT)
Participants will receive the investigator's choice of one of the following therapies:
- pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
- daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
- carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
- carfilzomib and dexamethasone (Kd) (28-day cycles)
干预措施: Carfilzomib (Drug)
Standard of Care Therapy (SOCT)
Participants will receive the investigator's choice of one of the following therapies:
- pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
- daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
- carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
- carfilzomib and dexamethasone (Kd) (28-day cycles)
干预措施: Bortezomib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to 4 years
PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.
Minimal Residual Disease (MRD) Complete Response (CR) Rate at 9 Months
时间窗: Up to 9 months
Minimal MRD is defined as the proportion of participants achieving CR/stringent CR (sCR) and MRD-negative status at 9 months. MRD negativity at 9 months is defined as negative MRD value at 9 months (± 3 months) in bone marrow assessment (\< 1 in 105 nucleated cells per IMWG criteria using NGS) (Kumar 2016). CR/sCR per IMWG criteria is determined by IRC.
Minimal Residual Disease (MRD) Complete Response (CR) Rate at 9 Months
时间窗: Up to 9 months
Minimal MRD is defined as the proportion of participants achieving CR/stringent CR (sCR) and MRD-negative status at 9 months. MRD negativity at 9 months is defined as negative MRD value at 9 months (± 3 months) in bone marrow assessment (\< 1 in 105 nucleated cells per IMWG criteria using NGS) (Kumar 2016). CR/sCR per IMWG criteria is determined by IRC.
Progression-Free Survival (PFS)
时间窗: Up to 4 years
PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.
次要结局
- CR Rate (CR/ Stringent Complete Response (sCR))(Up to 4 years)
- Overall MRD Negativity(Up to 7 years)
- Overall survival (OS)(Up to 7 years)
- Overall Response Rate (ORR)(Up to 7 years)
- MRD-negative CR/sCR(Up to 7 years)
- MRD-negative VGPR+(Up to 7 years)
- Sustained MRD Negativity(Up to 7 years)
- Duration of Response (DOR)(Up to 7 years)
- Time to Progression(Up to 7 years)
- Time to Next Treatment(Up to 7 years)
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(First dose up to 7 years)
- Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm)(Up to 7 years)
- Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)(Up to 7 years)
- Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score(Up to 7 years)
- Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score(Up to 7 years)
- Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score(Up to 7 years)
- Percentage of Participants Using Healthcare Resources(Up to 7 years)
- Overall MRD Negativity(Up to 7 years)
- MRD-negative CR/sCR(Up to 7 years)
- CR Rate (CR/ Stringent Complete Response (sCR))(Up to 4 years)
- Sustained MRD Negativity(Up to 7 years)
- Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)(Up to 7 years)
- Overall survival (OS)(Up to 7 years)
- Overall Response Rate (ORR)(Up to 7 years)
- MRD-negative VGPR+(Up to 7 years)
- Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score(Up to 7 years)
- Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score(Up to 7 years)
- Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score(Up to 7 years)
- Percentage of Participants Using Healthcare Resources(Up to 7 years)