Phase I/II Study to Evaluate the Safety and Tolerability, Radiation Dosimetry and Pharmacokinetics, and Efficacy of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.
研究概览
简要总结
This was a multicenter, open-label, phase I/II study to evaluate the safety and tolerability, radiation dosimetry and pharmacokinetic characteristics, and efficacy of [177Lu] Lu-XT033 injection in patients with metastatic prostate cancer, including a phase I study and a phase II extension study.
详细描述
The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period.
In phase I,Six subjects were enrolled in the 1.11 Gbq (30 mCi) group of [177Lu] Lu-XT033 Injection. The last subject in this group completed the 4-week observation period after the first dose, With the consent of the Safety Monitoring Committee (SRC), 6 subjects were enrolled in the 1.85 Gbq (50 mCi) group. Both groups used 8 ± 1 weeks as the dosing interval for a total of 4 doses.In phase II,Subjects who met the inclusion and exclusion criteria were treated with [177Lu] Lu-XT033 injection at the recommended phase II dose（RP2D）.After Cycle 4 treatment and prior to Cycle 5 treatment, the investigator assessed the following criteria to determine whether:
The patient showed evidence of response (i.e. radiological, PSA, clinical benefit)
The patient had signs of residual disease on CT with contrast/MRI or bone scan
The patient had shown good tolerance to the [177Lu] Lu-XT033 Injection
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Patients must have the ability to understand and sign an approved informed consent form (ICF).
- •Patients must be >= 18 and <＝80 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Patients must have a life expectancy >6 months.
- •Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- •Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive。
- •Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
- •Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone)； Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens.
- •Patients must have progressive mCRPC.
- •Patients must have adequate organ function。
- •Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, Intra-uterine device（IUD）,etc., during treatment and within 6 months of the last use of the trial drug.
排除标准
- •Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.
- •Known other malignancies.
- •Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment.
- •Known hypersensitivity to the components of the study therapy or its analogs.
- •A superscan as seen in the baseline bone scan.
- •Patients with a history of Central Nervous System (CNS) metastases.
- •Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.
结局指标
主要结局
For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.
时间窗: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
For phase I：Area Under plasma concentration-time Curve from time 0 to 168 hours (AUC0-168) of Lutetium [Lu 177] Lu-XT033 in patients.
时间窗: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC0-168 will be listed and summarized using descriptive statistics.
For phase I：Maximum plasma concentration (Cmax) of Lutetium [Lu 177] Lu-XT033 in patients.
时间窗: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
For phase I:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033 on dose 1.11Gbq and 1.85Gbq
时间窗: Through study completion, assessed up to 2 years.
To evaluate the safety and tolerability of \[177Lu\]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc
For phase I：Whole body and organ uptake of [177Lu]Lu-XT033 Injection
时间窗: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Quantitate the absorbed radiation doses (expressed as Gy/MBq) of administered \[177Lu\]Lu-XT033 to kidneys, liver, lungs, spleen, bone/red marrow and salivary glands.
For phase II:Prostate-specific Antigen 50 (PSA50) Response
时间窗: Through study completion, assessed up to 2 years.
PSA50 response was defined as the proportion of participants who had a \>= 50% decrease in PSA from baseline confirmed by a PSA measurement \>= 4 weeks later.
次要结局
- For phase I/II:Health related quality of life(HRQOL)(Through study completion, assessed up to 2 years.)
- For phase I/II:Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level(PCWG3)(Through study completion, assessed up to 2 years.)
- For phase I/II:Radiographic Progression-free Survival (rPFS)(Through study completion, assessed up to 2 years.)
- For phase I:Prostate-specific Antigen 50 (PSA50) Response(Through study completion, assessed up to 2 years.)
- For phase I/II: Duration of Response (DOR)(Through study completion, assessed up to 2 years.)
- For phase I/II:Time to First Symptomatic Skeletal Event (SSE)(Through study completion, assessed up to 2 years.)
- For phase I/II:Time to PSA progression(Through study completion, assessed up to 2 years.)
- For phase I/II:Overall Response Rate (ORR)(Through study completion, assessed up to 2 years.)
- For phase I/II:Disease Control Rate (DCR)(Through study completion, assessed up to 2 years.)
- For phase II:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033(Through study completion, assessed up to 2 years.)
- For phase I/II:Overall Survival (OS)(Through study completion, assessed up to 2 years.)