An Open-label Phase I, Dose-escalation Study to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Biodistribution, Radiation Dosimetry and Pharmacokinetics of BAY1862864 Injection in Subjects With Relapsed or Refractory CD22-positive Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 21
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose assessed by the number of subjects with dose-limiting toxicities (DLTs)
研究概览
简要总结
To establish a recommended dose of BAY1862864 Injection and to investigate how the study drug acts in the body, on the cancer cells and how safe it is in patients with advanced non-Hodgkin's lymphoma (NHL)
详细描述
The study will be divided into two parts: a "dose-escalation part" to evaluate safety profile and to explore the Maximum tolerated dose (MTD) and an "expansion part" to evaluate further the safety and tumor response profile of BAY1862864 Injection at the selected dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has relapsed or refractory CD22-positive histologically confirmed NHL
- •An archival paraffin-embedded tissue or fresh biopsy is available for the retrospective quantitative assessment of CD22 levels
- •Bone marrow involvement of cellular marrow with lymphoma determined to be < 25%
- •Subject has failed at least one prior chemo-/immunotherapy-based regimen
- •Life expectancy of at least 12 weeks
- •Not eligible for, or refused, or failed high-dose therapy combined with autologous stem cell rescue (HDT ASCR)
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- •Women of childbearing potential must have negative pregnancy test within seven days before the start of treatment
- •Subject was using adequate barrier birth control measures before the study and is willing to continue use of these during the entire course of the study and for the twelve months after the last administration of BAY1862864 Injection
- •Adequate bone-marrow, hepatic and renal function
- •Subject is capable of giving informed consent and has provided such consent in writing
排除标准
- •Previous exposure to the study drug. Previous exposure to CD22 antibody within six months before screening. Any radio-immunotherapy within six months before screening.
- •History of anaphylactic reactions to monoclonal antibody therapy. Known or suspected allergy or intolerance to any agent to be given in the course of this study.
- •Anti-cancer immunotherapy and/or anti cancer chemotherapy within four weeks before the first dose of study drug
- •Previous therapy with fludarabine-containing regimens within three months before screening
- •Participation in any other clinical trial in which the subject received active therapy within four weeks before the first scheduled dose of study drug
- •Any toxic effects (CTCAE ≥ Grade 2) of previous anti cancer therapy (incl. radiotherapy) that have not yet stabilized or significant post-treatment toxicities have been observed
- •Prior definitive radiotherapy completed less than four weeks before the date scheduled for first dose of BAY1862864
- •History of symptomatic metastatic brain or meningeal tumors. Presence of new or progressive brain metastases.
- •History of clinically significant cardiac disease
- •Clinically relevant findings in the ECG.
- •Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg and / or diastolic blood pressure > 100 mmHg, despite optimum medical management
- •History of arterial or venous thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or clinically relevant pulmonary embolism within three months before the first administration of BAY1862864 (except for adequately treated catheter-related venous thrombosis occurring more than one month before start of study medication)
- •Autologous bone-marrow transplant or stem-cell rescue within three months before the first administration of BAY1862864
- •Organ allograft (except for corneal transplant) or allogeneic bone-marrow transplant at any time before the first administration of BAY1862864
- •Positive result of hepatitis B virus (HBV-DNA) and/or human immunodeficiency virus antibody (HIV-Ab) test
- •Liver cirrhosis, defined as Child-Pugh class B or C
- •Any active infection of CTCAE Grade ≥2
- •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study
- •Major surgery or significant trauma within four weeks before the first administration of BAY1862864
- •Any treatment with biological response modifiers (such as, but not limited to, granulocyte colony-stimulating factor, G CSF), or any blood transfusion, within three weeks before first administration of BAY1862864
- •Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study result
- •Current pregnancy or breast-feeding
- •Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with study requirements
- •Close affiliation with the investigation site
- •Any use by the subject of illicit drugs or other substances that may, in the opinion of the investigator or his/her designated associate(s), have a reasonable chance of contributing to toxicity or otherwise confound the results
研究组 & 干预措施
Cohort 1b
Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 1.5 MBq (10 mg ACC).
干预措施: BAY1862864 (Drug)
Cohort 1a
Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 1.5 MBq (2 mg antibody chelator conjugate [ACC]).
干预措施: BAY1862864 (Drug)
Cohort 2
Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 3.1 MBq (10 mg ACC).
干预措施: BAY1862864 (Drug)
Cohort 3
Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 4.6 MBq (10 mg ACC).
干预措施: BAY1862864 (Drug)
Cohort 4
Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 6.1 MBq (10 mg ACC).
干预措施: BAY1862864 (Drug)
结局指标
主要结局
Maximum tolerated dose assessed by the number of subjects with dose-limiting toxicities (DLTs)
时间窗: Up to 6 weeks
次要结局
未报告次要终点