A Phase 2 Study of PHE885, B-cell Maturation Antigen (BCMA)- Directed CAR-T Cells in Adult Participants With Relapsed and Refractory Multiple Myeloma.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 146
- 试验地点
- 43
- 主要终点
- Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set
研究概览
简要总结
This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cell therapy, manufactured with a new process. The CAR-T cell therapy will be investigated as a single agent in relapsed and refractory multiple myeloma
详细描述
This clinical trial employs an open label, single arm, multi-center design with primary analysis testing overall response rate ( ORR), including one interim analysis for futility and one interim analysis for efficacy.
The trial population includes adult patients with relapsed and refractory multiple myeloma (MM) after failure of 3 or more lines of therapy, including failing an immunomodulatory drug (IMiD), a proteasome inhibitor (PI) and an anti-CD38 (cluster of differentiation 38) monoclonal antibody (mAb) and who have measurable disease at enrollment per IMWG criteria . In addition, patients must be refractory to the last line of therapy
The trial will enroll 90 efficacy evaluable adult patients with relapsed and refractory MM (efficacy evaluable means participants infused with a PHE885 product at target dose 10e6 that met all release specifications).
Patients will be followed for acute and intermediate safety and efficacy within this trial for a minimum of 2 years before being transferred to the long-term follow-up trial. A long-term post-study follow-up for lentiviral vector safety will be offered under a separate destination protocol for 15 years post injection per health authority guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age at the time of informed consent form (ICF) signature
- •Adult patients after failure of three or more lines of therapy including an IMiD (e.g., lenalidomide or pomalidomide), a proteasome inhibitor (e.g., bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g., daratumumab, isatuximab), and who have documented evidence of disease progression (IMWG criteria) 3, Must have received ≥2 consecutive cycles of treatment for at least three prior regimens unless deemed refractory to that regimen (i.e., progressive disease as the best response)
- •4. Must be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen).
- •5. Measurable disease at enrollment as defined by the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
- •Must have a leukapheresis material of non-mobilized cells accepted for manufacturing
排除标准
- •1.Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy. 2.Participants who have received prior BCMA -directed bi-specific antibodies or anti-BCMA antibody drug conjugate.
- •3. Prior autologous SCT within 3 month or allogenic SCT within 6 months prior to signing informed consent.
- •4.Plasma cell (PC) leukemia and other plasmacytoid disorders, other than MM 5.POEMS syndrome 6.Active central nervous system (CNS) involvement by malignancy 7.Patients with active neurological autoimmune or inflammatory disorders 8.Inadequate cardiac, renal, hepatic or hematologic function as defined in the protocol.
- •Other protocol-defined Inclusion/Exclusion may apply.
研究组 & 干预措施
PHE885
Patients will receive PHE885
干预措施: PHE885 (Biological)
结局指标
主要结局
Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set
时间窗: 24 Months
Percentage of patients with best overall response (BOR) of either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) according to the International Myeloma Working Group (IMWG) criteria'
次要结局
- Transgene of PHE885 concentrations over time in peripheral blood and bone marrow(24 Months)
- Cellular kinetics parameter: AUC(24 months)
- Key Secondary End point: MRD Negativity rate in Bone Marrow(24 months)
- Time to next anti-myeloma treatment (TTNT)(24 Months)
- Overall Survival (OS)(24 Months)
- Patient Reported Outcomes (PRO): EORTC-QLQ-MY20(24 months)
- Cellular kinetics parameter: Tmax(24 Months)
- Complete response rate (CRR)(24 Months)
- Progression free survival (PFS)(24 Months)
- Patient Reported Outcomes (PRO): EORTC-QLQ-C30(24 months)
- Manufacturing turnaround time(24 months)
- Time to response(24 Months)
- Duration of Response (DOR)(24 Months)
- Durability of Minimal Residual Disease (MRD)negativity(24 Months)
- Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire(24 months)
- PHE885 manufacturing success rate(24 Months)
- Immunogenicity to PHE885(24 Months)
- Cellular kinetics parameter: Cmax(24 Months)