jRCT2041230077招募中不适用
A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects with B-Cell Non-Hodgkin Lymphoma
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 317
- 主要终点
- objective response rate (ORR)
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 分配方式
- Single Arm Study
- 干预模型
- Single Assignment
- 主要目的
- Treatment Purpose
- 盲法
- Open(masking Not Used)
入排标准
- 年龄范围
- 18age old over 至 No limit（—）
- 性别
- All
入选标准
- •Subject is between 18 and 80 years of age at the time of ICF signing. Those subjects >80 years of age may enroll in elderly cohorts.
- •Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
- •For RR cohorts: Subject has received at least 2 lines of therapy to which the subject has been either refractory or has subsequently relapsed. In order to be eligible for the RR cohorts in this study subjects must not be candidates for treatment regimens known to provide clinical benefit in B-NHL.CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T-cell therapies.
- •For 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria.
- •Radiation to localized disease prior to study entry is allowed. The last dose of radiation should not be within 14 days prior to the first dose of AZD
- •The subject should have recovered from all radiation-induced toxicity prior to the first dose of AZD
- •Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of <=
- •Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received).
- •Subject must have at least 1 measurable disease site.
- •Subject must have ANC >= 1000/mm3, platelets >= 50,000 mm3, hemoglobin >= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening.
- •Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN.
- •Subject must have an eGFR >= 50mL/min as estimated by the MRD formula.
- •Subject is capable of understanding and complying with the parameters as outlined in the protocol and able to sign informed consent.
排除标准
- •Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
- •Subject has a active central nervous system (CNS) involvement by their B-NHL.
- •Subject has a history of leukemic presentation (>5,000 circulating lymphoma cells/micro L in the peripheral blood) of their B-NHL.
- •Subject has a history or presence of clinically significant CNS pathology.
- •Subject has CNS involvement from active or history of autoimmune disease.
- •Subject experienced Grade >= 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
- •Subject experienced Grade >= 2 neurotoxicity following prior TCE or CAR T-cell therapy.
- •Subject has received another investigational drug within 5x T1/2 (of this agent) within 28 days of enrollment, whichever is shorter.
- •Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
- •Subject received CD19 CAR T therapy within 3 months prior to first dose.
- •Subject requires chronic immunosuppressive therapy (including steroids >10mg prednisone/day). A short course of corticosteroids for symptom and disease control prior to first dose of study treatment is allowed. Immunosuppressive therapy must be discontinued 14 days or 5 half-lives prior to the first dose of study treatment (whichever is shorter).
- •Subject has any medical or psychiatric condition which, in the opinion of Investigator or medical monitor, places subject at an unacceptable high risk of toxicity or could interfere with successful or safe delivery of therapy or evaluation of drug in subject safety or study results.
- •Subject has received any therapy to treat cancer (including radiation, chemotherapy biologics or cellular therapies) or undergone a major surgical procedure within 14 days (or within 5 half-lives of an anti-cancer drug prior to first dose of study treatment, whichever is shorter. For RR disease only: The administration of debulking chemotherapy outside of this washout period to reduce the risk of TLS or CRS / NT in subjects with bulky disease is permitted.
- •Subject has known serious infection requiring treatment.
- •Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
- •Subject has a history of major cardiac abnormalities.
- •If female, subject must not be pregnant or breastfeeding.
- •Subject has unresolved AEs >= Grade 2 from prior anticancer therapy except for:
- •Alopecia, Peripheral neuropathy, Anemia or thrombocytopenia
结局指标
主要结局
objective response rate (ORR)
defined as CR + PR
clinical benefit rate (CBR)
时间窗: 24 weeks
defined as CR + PR + MR + SD for 24 weeks
Concentrations of AZD0486 and antidrug antibody (ADA)
时间窗: designated time points throughout the study
will be determined at designated time points throughout the study
PK parameters of AZD0486
时间窗: after infusion in Cycle 1
including the Cmax, the time to Cmax (Tmax), AUC from time 0 to the time of the last measurable concentration (AUCt), clearance (CL), the terminal phase elimination rate constant, and terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods
Exploratory research variables
Exploratory research will be conducted to study exposure-response relationships via biomarker relationships with PK, safety, and clinical activity
Adverse events
时间窗: until the 90-day post-last treatment visit or until a new line of therapy is initiated, whichever occurs earlier
Adverse events will be graded according to the NCI CTCAE, version 5.0
次要结局
未报告次要终点
研究者
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