Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 96
- 试验地点
- 9
- 主要终点
- Incidence of Dose limiting toxicities (DLT)
研究概览
简要总结
This was a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells were investigated as a single agent in multiple myeloma
详细描述
This was a phase I, open label study to characterize the safety and tolerability of a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) manufactured with a new process. In the dose escalation part (Part A) of the study, the anti-BCMA CAR-T cell therapy was studied in adult multiple myeloma (MM) subjects who were relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy was studied in newly diagnosed adult subject with MM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A: Subjects with MM who are relapsed and/or refractory to at least 2 prior treatment regimens, including an IMiD (e.g. lenalidomide or pomalidomide), a proteasome inhibitor (e.g. bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g. daratumumab), if available, and have documented evidence of disease progression (IMWG criteria)
- •Part A: ECOG performance status that is either 0 or 1 at screening
- •Part B: Subjects with newly diagnosed multiple myeloma (NDMM) who have received a minimum of 4 and up to 6 cycles of standard induction therapy with VRd, D-VRd, or D-Rd, and have achieved a response of PR or better. One cycle of CyBorDex is allowed prior to induction.
- •Part B: ECOG performance status that is either 0,1 or 2 at screening
- •Measurable disease as defined by the protocol
- •Adequate hematological values
- •Must have a leukapheresis material of non-mobilized cells accepted for manufacturing
排除标准
- •Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy. Patients who have received prior BCMA-directed bi-specific antibodies or antibody-drug conjugates (ADC) are not excluded.
- •Autologous HSCT within 6 weeks prior to enrollment or any prior history of allogeneic hematopoietic stem cell transplant (HSCT)
- •Chemotherapy or any concomitant anti-cancer therapies (other than protocol prescribed lymphodepletion (LD) chemotherapy) within 2 weeks prior to apheresis
- •Treatment with small molecule targeted antineoplastics within 2 weeks of apheresis collection or 5 half-lives whichever is shorter
- •Have received antibodies or immunotherapies (other than daratumumab) within 4 weeks prior to apheresis collection. Daratumumab within 3 weeks prior to apheresis collection.
研究组 & 干预措施
PHE885 (Part B)
Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.
干预措施: PHE885 (Biological)
PHE885 (Part A)
Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.
干预措施: PHE885 (Biological)
结局指标
主要结局
Incidence of Dose limiting toxicities (DLT)
时间窗: 28 days
Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 24 months
Nature of Dose limiting toxicities (DLT)
时间窗: 28 days
Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
次要结局
- DOR (duration of response) in Part A(from disease response to disease progression, assessed up to approximately 24 months)
- Overall Complete Response Rate (CRR) in Part A(24 months)
- Overall CRR in Part B(24 months)
- Overall Response Rate (ORR) in Part A(24 months)
- ORR in Part B(24 months)
- Response rate at 3 and 6 months in Part A(3 months, 6 months)
- Tmax of BCMA CAR-T cells(24 months)
- Clast of BCMA CAR-T cells(24 months)
- Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)(24 Months)
- Overall response rate at 3 and 6 months in Part B(3 months, 6 months)
- Cmax of BCMA CAR-T cells(24 months)
- AUC of BCMA CAR-T cells(24 months)
- number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy(24 Months)
- CRR at months 3 and 6 in Part A(3 months, 6 months)
- CRR at months 3 and 6 in Part B(3 months, 6 months)
- DOR in Part B(from disease response to disease progression, assessed up to approximately 24 months)