A Phase 2, Multi-cohort, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With Clinical High-Risk Multiple Myeloma (KarMMa-2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 312
- 试验地点
- 25
- 主要终点
- Overall response rate (ORR)- Cohort 1
研究概览
简要总结
This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in participants with relapsed and refractory multiple myeloma (RRMM) (Cohort 1), in participants with RRMM who receive bridging therapy with talquetamab (Cohort 1b), in participants with multiple myeloma (MM) having progressed within 18 months of initial treatment with autologous stem cell transplantation (ASCT) (Cohort 2a) and without ASCT (Cohort 2b) or, in participants with inadequate response post ASCT during initial treatment (Cohort 2c) and the efficacy and safety of bb2121 used in combination with lenalidomide maintenance in participants with suboptimal response post ASCT (Cohort 3). Approximately 248 participants will be enrolled into one of three cohorts. Cohort 1 (including cohort 1b) will enroll approximately 126 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.
详细描述
Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only. In Cohort 1b only, subjects will receive bridging therapy with 1 to 2 cycles of talquetamab, and initiate Lymphodepleting (LD) chemotherapy at least 14 days after the last dose of talquetamab.
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
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
- •For Cohorts 1 and 2 only, participant has measurable disease, defined as:
- •M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
- •Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Subjects with one of the following cohort specific requirements:
- •Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
- •Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
- •Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
- •Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
- •Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
- •Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen
- •Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
- •Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
- •Subject must have the following HR factors:
- •Early relapse defined as:
- •Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.
- •Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance.
- •Cohort 3 participants with newly diagnosed MM (NDMM) who received only induction and ASCT, without subsequent consolidation or maintenance Cohort 3
- •Must have received 4 to 6 cycles of induction therapy which must contain at minimum, a proteasome inhibitor and an immunomodulatory agent and must have had single ASCT within 6 months prior to consent
- •Must have achieved documented PR or VGPR at first post-ASCT assessment approximately 100 days after ASCT and this response must be maintained at screening
- •Per Investigator's assessment, subject must be a candidate for single-agent lenalidomide maintenance
- •Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent
- •Subject received any of the following within the last 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent:
- •Plasmapheresis
- •Major surgery (as defined by the investigator)
- •Radiation therapy other than local therapy for myeloma associated bone lesions
- •Use of any systemic anti-myeloma drug therapy
- •Subject with known central nervous system involvement with myeloma
- •Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
- •History or presence of clinically relevant central nervous system (CNS) pathology
- •Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
- •Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
- •Ongoing treatment with chronic immunosuppressants
- •Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
- •Subject has received ASCT within 12 weeks prior to leukapheresis
- •Subject has history of primary immunodeficiency
- •Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C
- •Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
- •Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years
- •Pregnant or lactating women
- •Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab
- •Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 6 months prior to consent (For Cohort 3)
- •For Cohort 1b, previous treatment with any G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) targeted therapy or T-cell engagers
- •For Cohort 1b, known allergies, hypersensitivity, or intolerance to talquetamab or its excipients
研究组 & 干预措施
Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants
bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy
干预措施: bb2121 (Biological)
Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants
干预措施: bb2121 (Biological)
Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants
干预措施: Talquetamab (Drug)
Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants
干预措施: bb2121 (Biological)
Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants
干预措施: bb2121 (Biological)
Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT
干预措施: bb2121 (Biological)
Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma
干预措施: bb2121 (Biological)
Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma
干预措施: Lenalomide (Drug)
结局指标
主要结局
Overall response rate (ORR)- Cohort 1
时间窗: Up to approximately 5 years (Participants will transition to the long term follow-up (LTFU) study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
Complete response (CR) rate - Cohort 1b, 2a, 2b, 2c, and Cohort 3
时间窗: Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit)
Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
次要结局
- Complete response (CR) rate - Cohort 1(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Overall response rate (ORR) - Cohort 1b, 2a, b, c and Cohort 3(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Very good partial response (VGPR) rate - Cohort 2c(Up to approximately 5 years(Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Time to response (TTR)(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Duration of response (DoR)(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Progression-free survival (PFS)(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Time to progression (TTP)(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Overall survival (OS)(Up to approximately 5 years (Participants will transition to the LTFU study after a minimum of 12 months post-infusion for Cohorts 1, 2a, 2b, and 2c; and after a minimum of 6 months post-infusion for Cohort 1b, at their next visit))
- Percentage of participants who received lenalidomide maintenance for the first 3 cycles following bb2121 infusion with at least 75% dose compliance - Cohort 3(Up to 3 months)
- Pharmacokinetics - Cmax(Minimum 5 years after bb2121 infusion)
- Pharmacokinetics - tmax(Minimum 5 years after bb2121 infusion)
- Pharmacokinetics - AUC(Minimum 5 years after bb2121 infusion)
- Pharmacokinetics - tlast(Minimum 5 years after bb2121 infusion)
- Pharmacokinetics - AUC0-28days(Minimum 5 years after bb2121 infusion)
- Immunogenicity(Minimum of 2 years after bb2121 infusion)
- Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30)(Minimum 5 years after bb2121 infusion)
- Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire(Minimum 5 years after bb2121 infusion)
- Subject-reported outcomes as measured by EORTC-QLQ-MY20(Minimum 5 years after bb2121 infusion)