An Open-label, Phase 1, First in Human Study Investigating the Safety, Tolerability, Pharmacokinetics and Efficacy of NVG-111 in Subjects With Relapsed/Refractory ROR1+ Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 3
- 主要终点
- Laboratory safety abnormalities
研究概览
简要总结
NVG-111 is a bispecific antibody drug, having two "arms", one arm attaches to a substance on cancer cells called ROR1, the other arm attaches to the body's immune cells directing them to kill the cancer cells. This is the first clinical trial of the drug NVG-111, and will include patients with certain types of cancer including chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma (SLL) mantle cell lymphoma (MCL), follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) in Group A. Subjects with solid tumours, focusing initially on stage IV non-small cell lung cancer (NSCLC) or malignant melanoma.
详细描述
Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is a protein which is expressed at high levels on many types of cancers but is absent or expressed at low levels in normal adult organs. NVG-111 is a bispecific antibody T cell engager, comprising tandem single chain variable fragments (scFv), one arm binding to ROR1 on cancer cells, the other to cell surface CD3 on lymphocytes. Dual binding of NVG-111 causes MHC-independent immunological synapse formation, releasing perforins, granzyme B and cytokines, resulting in targeted killing of the cancer cells.
This is a Phase 1 first in human study to assess the safety, pharmacokinetics and efficacy of NVG-111 in patients with subjects with relapsed/refractory ROR1+ malignancies.
A range of doses will be studied in sequential cohorts to understand safety, pharmacokinetics and pharmacodynamics of the drug and establish the recommended phase 2 dose (RP2D). At each dose level, patients will receive 3 cycles of NVG-111 by continuous intravenous infusion, each cycle consists of 21 days treatment. Additional cycles may be given depending on the response seen.
All patients will have a safety follow up visit 4 weeks after completion of treatment with NVG-111, and will then enter long term follow up for up to two years to evaluate the duration of efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- •Richter's transformation.
- •CNS or leptomeningeal active disease.
- •High tumour bulk as defined in the protocol.
- •Allogeneic or autologous organ transplant within prior 6 months.
- •Uncontrolled autoimmune haemolytic anaemia or idiopathic thrombocytopenic purpura within 8 weeks of screening.
- •Clinically significant neurological disease.
- •Clinically significant cardiovascular disease or ECG abnormalities.
- •Severe chronic lung disease.
- •Positive test at Screening for HIV, hepatitis B or hepatitis C infection.
- •Any other concurrent cancer or cancer treatments.
- •Uncontrolled ongoing infection
- •Recent major surgery
- •Concurrent participation in another clinical trial, or experimental therapy within 5 half-lives of Screening
- •Pregnant or currently breastfeeding.
- •Any other medical condition that in the opinion of the investigator contraindicates participation in the study.
研究组 & 干预措施
Group A: Haematological malignancies
干预措施: NVG-111 (Drug)
Group B: Solid tumours
干预措施: NVG-111 (Drug)
结局指标
主要结局
Laboratory safety abnormalities
时间窗: Up to 10 months
Safety parameter assessed by absolute values and change from baseline in laboratory safety assessments
Changes from baseline in ECOG
时间窗: Up to 10 months
Safety parameter assessed by change from baseline in ECOG performance status
Number of serious adverse events (SAEs)
时间窗: Up to 10 months
Safety parameter defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or is medically significant/important
Number of adverse events of special interest (AESI)
时间窗: Up to 10 months
Safety parameter: specific protocol-defined AEs of Grade \>=3
Vital sign abnormalities
时间窗: Up to 10 months
Safety parameter assessed by absolute values and change from baseline in vital signs
ECG abnormalities
时间窗: Up to 10 months
Safety parameter assessed by absolute value and change from baseline in ECG intervals including QTcF
Number of treatment-emergent adverse events (TEAEs)
时间窗: Up to 10 months
Safety parameter assessed by: type, frequency, severity and treatment-relatedness of AEs following commencement of dosing
Number of dose limiting toxicities (DLTs)
时间窗: Up to 28 days
Safety parameter assessed by protocol-defined adverse events
次要结局
未报告次要终点