A Phase I, Single Centre, Open-label Study of TLX592 to Assess the Safety and Tolerability, Pharmacokinetics, Biodistribution and Radiation Dosimetry in Patients Diagnosed With Prostate Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
研究概览
简要总结
This is a Phase 1 trial of TLX592, a humanised, engineered monoclonal antibody HuX592r conjugated with a DOTA chelator and radiolabelled with 64Cu (64Cu-TLX592). TLX592 is being developed as a PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment of PSMA-expressing tumours, therefore this study has been designed to assess the safety and tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of 64Cu-TLX592.
详细描述
The optimisation dose and imaging conditions will be conducted in prostate cancer patients with with oligometastatic disease ( (defined as 5 sites or less outside of the prostate bed). On determining the optimal dose and imaging conditions, an additional cohort of patients with a higher tumour burden such as multiple metastatic sites across ≥10 regions will be assessed.
Study conduct:
Nine, prostate cancer patients with oligometastatic disease as detected using 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CT scanning (defined as 5 sites or less outside of the prostate bed) will be randomised to one of three treatment groups to receive a single injection of:
- Group 1: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu.
- Group 2: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 8mg of unlabelled TLX592 (mass dose of 10mg).
- Group 3: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 18mg of unlabelled TLX592 (mass dose of 20mg). If one of the three patients in a specific group experiences a dose-limiting toxicity, three more patients will be treated at the same dose level.
Patients with a higher tumour burden such as multiple metastatic sites across ≥10 regions [regions: prostate bed, pelvic lumph nodes, skeleton, distant sites (including viscera)] as detected on 68Ga-PSMA or 18F-DCFPyl PMSA imaging agent will be allocated to a fourth group.
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
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Biochemically recurrent metastatic adenocarcinoma of the prostate, or metastatic primary adenocarcinoma of the prostate.
- •Histologically or cytologically confirmed diagnosis of adenocarcinoma of prostate.
- •PSMA-expressing prostate adenocarcinoma as seen on 68Ga-PSMA-11 or 18F- DCFPyl PSMA PET/CT scanning within the last 1 month showing PSMA-avid disease.
- •ECOG performance status of 0 -
- •Normal organ function and marrow reserve:
- •White blood cell (WBC) count ≥ 2.5 x 109/L or absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
- •Platelets ≥ 100 x 109/L.
- •Haemoglobin ≥ 90g/L.
- •Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin).
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.0 x ULN (or
- •5.0 x ULN in the presence of liver metastases).
- •Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min.
排除标准
- •A patient is excluded from participation in the trial if one or more of the following criteria are met:
- •Known active brain metastases.
- •Serious active infection (as assessed by investigator).
- •Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or haematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
- •Known or suspected allergies, hypersensitivity, or intolerance to the IMP or its excipients.
- •Other investigational agents within 4 weeks of randomization.
- •Radiotherapy or immunotherapy within 4 weeks prior to the planned administration of 64Cu-TLX592 or continuing adverse effects (> grade 1) from such therapy [Common Terminology Criteria for Adverse Events (CTCAE) version 5].
- •Previous administration of any radionucleotide within 10 half-lives of 64Cu.
- •Inability to understand, or unwilling to sign, a written informed consent document or to follow investigational procedures in the opinion of the investigator.
- •Patients who are unable to maintain self-care.
研究组 & 干预措施
Dose level 1 of 64Cu-TLX592
Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu
干预措施: 64Cu-DOTA-TLX592 (Drug)
Dose level 2 of 64Cu-TLX592
Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 8mg of unlabelled TLX592 (mass dose of 10mg).
干预措施: 64Cu-DOTA-TLX592 (Drug)
Dose level 3 of 64Cu-TLX592
Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 18mg of unlabelled TLX592 (mass dose of 20mg).
干预措施: 64Cu-DOTA-TLX592 (Drug)
Confirmation of optimal 64Cu-TLX592 dose
Based on the result of Groups 1-3, the optimal dose and imaging timepoints will be selected to treat 3 patients with higher tumour burden (≥10 metastatic sites and/or visceral disease as detected on a 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CT scan).
Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 0, 8 or 18mg of unlabelled TLX592.
干预措施: 64Cu-DOTA-TLX592 (Drug)
结局指标
主要结局
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
时间窗: Day 1 to 28
Treatment emergent adverse events (TEAE) will be classified according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to NCI CTCAE V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE v.5.0
Pharmacokinetics of 64Cu-TLX592
时间窗: Day 1-4 after a single administration of 64Cu-TLX592
Patient plasma samples at 0h, 1h, 4 ± 0.5h, 20 ± 4h and 48 ± 4h after the administration of 64Cu-TLX592 will be counted for radioactivity.
Dosimetry of 64Cu-TLX592
时间窗: Up to 5 days after a single administration of 64Cu-TLX592
For dosimetry analysis, biodistribution whole body PET/CT imaging will be performed at 1h, 4 ± 0.5h, 20 ± 4h, with the option for a an additional two scans to be performed between the 36-120 hours.
Biodistribution of 64Cu-TLX592
时间窗: Up to 24h after a single administration of 64Cu-TLX592
On Days 0, Day 1 and potentially at 36-120h after administration of the investigational product, the biodistribution and tumour imaging will be performed. An end of study visit will be conducted on Day 28 ± 2 days. 64Cu-TLX592 images will be centrally analysed for absorbed organ and whole body doses in a standardised fashion. In addition, tumour absorbed doses will be determined for scientific purposes (estimation of achievable tumour doses of therapeutic nuclides labelled to TLX592)
次要结局
- Optimal antibody dose of TLX592(Single diagnostic administration 1 day, followed by a diagnostic scan on Day 1)
- Comparison of PSMA-targeting of different PMSA-imaging agents(Single diagnostic administration 1 day, followed by a diagnostic scan on Day 1.)