A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 255
- 试验地点
- 86
- 主要终点
- Parts A & B: Safety Evaluation of AZD0486
研究概览
简要总结
This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimization study of surovatamig (AZD0486) to evaluate the safety, tolerability, and efficacy of surovatamig (AZD0486) monotherapy in participants with R/R B ALL. The study will consist of 4 parts. Part A: monotherapy dose escalation in 3L+ B-ALL. Part B: dose optimization in 3L+ B-ALL. Part C: Dose expansion in 3L+ B-ALL. Part D: Dose optimization and efficacy expansion in R/R B-ALL (2L+)
详细描述
This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of surovatamig (AZD0486) monotherapy in r/r B-ALL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 12 years and above (Parts A, B, C and D).
- •Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:
- •Bone marrow infiltration with >/= 5% blasts
- •Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option (Parts A, B, C); or relapsed or refractory to ≥1 prior line of therapy (Part D).
- •Philadelphia positive participants are allowed in all parts of the study, if intolerant or refractory to TKIs.
- •For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
- •For Participants 16 years or younger, Lansky score more or equal to 50%.
- •The above is a summary, other inclusion criteria details may apply.
排除标准
- •Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria), or signs of CNS involvement.
- •Isolated extramedullary disease relapse.
- •Testicular leukemia
- •History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
- •History of other malignancy (with certain exceptions).
- •Unresolved AEs >/= Grade 2, from prior therapies
- •Prior therapy with ADCs within 3 weeks, TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
- •GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.
- •The above is a summary, other exclusion criteria details may apply.
研究组 & 干预措施
Part A: AZD0486 Dose Escalation
Ascending dose level cohorts of surovatamig (AZD0486) in B-ALL participants aged 12 years and above.
干预措施: Surovatamig (Drug)
Part B: Dose Optimization
Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12 years and above, will receive surovatamig (AZD0486) IV infusions and will be randomized in a 1:1 ratio.
干预措施: Surovatamig (Drug)
Part C: Dose Expansion
Part C will consist of 1 cohort of participants aged 12 years and above, treated with the optimal dose selected in Part B and receive IV surovatamig (AZD0486) monotherapy.
干预措施: Surovatamig (Drug)
Part D: Dose Optimization and Efficacy Expansion in 2L+
Part D will enroll participants aged 12 years and above with Ph(+) and Ph(-) B-ALL relapsed/refractory to ≥1 prior line of therapy. Participants will be randomized 1:1 to 2 dose levels of surovatamig IV.
干预措施: Surovatamig (Drug)
结局指标
主要结局
Parts A & B: Safety Evaluation of AZD0486
时间窗: From signing of informed consent through data cutoff, up to 57 months
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
Part D: CR/CRh within 3 cycles
时间窗: Up to three cycles of 28 days each
To evaluate the efficacy of surovatamig in Part D based on NCCN response criteria. CR/CRh is defined as a best response of CR/CRh within 3 cycles.
Part A: Frequency of DLTs
时间窗: Up to 28 days
DLTs are dose-limiting toxicities as defined in the study protocol
Parts A & B: Safety Evaluation of AZD0486
时间窗: From signing of informed consent through data cutoff, up to 42 months
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
Parts B & C: Rate of CR within 3 cycles
时间窗: Up to three cycles of 28 days each
To evaluate the efficacy of surovatamig based on NCCN response criteria (in Part B and C).
次要结局
- Parts A, B, C, D: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study(From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 57 months)
- Parts A, B, C, D: Duration of CR/CRh(From first dose to last progression or data cutoff, whichever comes first, assessed up to 57 months)
- Parts A, B, C, D: Event-free survival (EFS)(From First dose to last progression or data cutoff, whichever comes first, assessed up to 57 months)
- Parts A, B, C, D: Overall Survival (OS)(From First dose to data cutoff, up to 57 months)
- Parts B, C & D: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute(From first dose to EOT, up to 57 Months)
- Part A, B, C, D: MRD-negative rate of CR, CR/CRh and CR/CRh/CRi(From First dose to data cutoff, up to 57 months)
- Parts A, B, C, & D: PK characterization of suravatomig(From first dose to data cutoff, up to 57 months)
- A, B, C, & D: PK Characterization of suravatomig(From first dose to data cutoff, up to 57 months)
- A, B, C, & D: PK Characterization of surovatamig(From first dose to data cutoff, up to 57 months)
- Parts A, B, C, D: ADA characterization of suravatomig(From First dose to EOT, up to 57 months)
- Part C, D: Safety Evaluation of suravatomig(From signing of informed consent through completion of study treatment, an average of 6 months)
- Part D: Rate of CR and CR/CRh/CRi within 3 cycles(Up to 3 cycles of 28 days each)
- Part A: Rate of CR within 3 cycles(Up to 3 cycles of 28 days each)
- Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles(Up to 3 cycles of 28 days each)
- Parts A, B, C: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study(From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 42 months)
- Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi(From first dose to last progression or data cutoff, whichever comes first, assessed up to 42 months)
- Parts A, B, C: Event-free survival (EFS)(From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months)
- Parts A, B, C: Overall Survival (OS)(From First dose to data cutoff, up to 42 months)
- Parts B &C: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute(From first dose to EOT, up to 42 Months)
- Part A, B, C:MRD-negative rate of CR(From First dose to data cutoff, up to 42 months)
- Parts A, B, & C: PK characterization of AZD0486(From first dose to data cutoff, up to 42 months)
- Parts A, B & C: PK Characterization of AZD0486(From first dose to data cutoff, up to 42 months)
- Parts A, B, C: ADA characterization of AZD0486(From First dose to EOT, up to 42 months)
- Part C: Safety Evaluation of AZD0486(From signing of informed consent through completion of study treatment, an average of 6 months)
- Parts A, B, C: PK Characterization of AZD0486(From first dose to data cutoff, up to 42 months)