A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of Rondecabtagene Autoleucel, a CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy in Participants With Aggressive B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 46
- 主要终点
- Phase 1: Evaluate the safety and tolerability of a single dose of LYL314 administered as a single agent
研究概览
简要总结
This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of rondecabtagene autoleucel (ronde-cel) also known as LYL314, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.
详细描述
This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of ronde-cel, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.
Five cohorts of participants will be enrolled:
Cohort 1: (3rd or later line, 3L+) Participants who have received least two prior lines of treatment
Cohort 2: (CAR T-cell experienced, 3L+): Participants who have received at least two prior lines of treatment including one prior CAR T.
Cohort 3: (second line, 2L) Participants with refractory disease or relapse within one year of first-line therapy (second-line).
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 (Outcomes Assessor)
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
- •Age 18 years or older
- •Willing and able to provide written informed consent
- •Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
- •Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
- •Relapsed or refractory disease.
- •At least 1 measurable lesion (per Lugano classification)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
- •Absolute neutrophil count (ANC) ≥ 1000/µL
- •Platelet count ≥ 50,000/µL
- •Absolute lymphocyte count (ALC) ≥ 200/µL
- •Other protocol-defined criteria apply.
排除标准
- •History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
- •Active central nervous system involvement
- •History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
- •Ongoing or impending oncologic emergency
- •Recent systemic anti-cancer therapy or radiation
- •Ongoing non-hematologic toxicities due to prior therapy
- •History of allogeneic stem cell or solid organ transplantation
- •Autologous stem cell transplantation within 6 weeks
- •History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel) (Cohort 2).
- •Primary immunodeficiency
- •History of autoimmune disease resulting in end organ injury or requiring recent therapy
- •Other protocol-defined criteria apply.
研究组 & 干预措施
Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
Single dose determined during Phase 1.
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)
干预措施: Rondecabtagene autoleucel (ronde-cel) (Drug)
Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)
干预措施: Fludarabine (Drug)
Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
Single dose determined during Phase 1.
干预措施: Fludarabine (Drug)
Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)
干预措施: Cyclophosphamide (Drug)
Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)
干预措施: Fludarabine (Drug)
Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)
干预措施: Cyclophosphamide (Drug)
Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)
干预措施: Fludarabine (Drug)
Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)
干预措施: Cyclophosphamide (Drug)
Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)
干预措施: Cyclophosphamide (Drug)
Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)
干预措施: Fludarabine (Drug)
Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
Single dose determined during Phase 1.
干预措施: Cyclophosphamide (Drug)
Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)
干预措施: Fludarabine (Drug)
Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Phase 1: Evaluate the safety and tolerability of a single dose of LYL314 administered as a single agent
时间窗: Baseline to Month 24
Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)
Phase 2: Estimate the efficacy of LYL314, as measured by ORR
时间窗: Baseline to Month 24
ORR based on Independent Review Committee (IRC) assessment per Lugano criteria
Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent
时间窗: Baseline to Month 24
Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)
Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR)
时间窗: Baseline to Month 24
ORR based on Independent Review Committee (IRC) assessment per Lugano criteria
次要结局
- Phase 1: Evaluate the efficacy of ronde-cel(Baseline to Month 24)
- Phase 1: Evaluate the feasibility of treatment with ronde-cel(Baseline to Month 24)
- Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent(Baseline to Month 24)
- Phase 2: Estimate the efficacy of ronde-cel(Baseline to Month 24)
- Phase 2: Estimate the efficacy of ronde-cel(Baseline to Month 72)
- Phase 2: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent(Baseline to Month 24)
- Phase 2: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent(Baseline to Month 24)
- Phase 1: Evaluate the efficacy of LYL314(Baseline to Month 24)
- Phase 1: Evaluate the feasibility of treatment with LYL314(Baseline to Month 24)
- Phase 1: Evaluate the pharmacokinetics of LYL314 when administered as a single agent(Baseline to Month 24)
- Phase 2: Estimate the efficacy of LYL314(Baseline to Month 72)
- Phase 2: Evaluate the safety and tolerability of a single dose of LYL314 administered as a single agent(Baseline to Month 24)
- Phase 2: Evaluate the pharmacokinetics of LYL314 when administered as a single agent(Baseline to Month 24)