A Phase 1/2 Dose Escalation Trial With Administration Schedule Exploration Evaluating Single Agent TD001, a PSMA-Targeted Antibody-Drug Conjugate, in Patients With PSMA-Expressing Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 7
- 主要终点
- Recommended Phase 2 doses (dose escalation)
研究概览
简要总结
This study will evaluate the safety, tolerability, drug levels (pharmacokinetics) and preliminary antitumor activity of TD001, an antibody-drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA), in men with metastatic PSMA-expressing castration-resistant prostate cancer (CRPC).
详细描述
This is a first-in-human, open-label, multicenter Phase 1/2 study with a dose escalation part to determine recommended Phase 2 doses (RP2Ds) of TD001 for further evaluation in an expansion part of the study. Multiple dosing schedules may be evaluated. The safety and preliminary efficacy endpoints of this study will support dose optimization in this patient population.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Patient must fully understand the study requirements and voluntarily sign informed consent.
- •PSMA-expressing metastatic CRPC with documented progression based on serum PSA, RECIST 1.1 with PCWG3, and/or bone disease.
- •At least one measurable metastatic lesion per RECIST 1.
- •Adequate organ function.
- •Prior orchiectomy and/or ongoing androgen deprivation therapy.
- •Prior treatment with at least one androgen receptor pathway inhibitor (ARPI) drug.
排除标准
- •Previous treatment with strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, or hemi-body irradiation, within 6 months before treatment.
- •Systemic anticancer therapy including an investigational agent within 28 days before treatment.
- •Known hypersensitivity to the components of TD001, its analogs, or excipients.
- •Current dyspnea at rest, other disease requiring continuous oxygen therapy, or history of pneumonitis
研究组 & 干预措施
Dose escalation
Sequential groups of participants receive TD001 at escalating doses
干预措施: TD001 (Drug)
RP2D dose expansion
Groups of participants receive TD001 at the recommended Phase 2 doses (RP2Ds)
干预措施: TD001 (Drug)
结局指标
主要结局
Recommended Phase 2 doses (dose escalation)
时间窗: Treatment + follow-up (estimated 9 months)
Incidence of AEs, SAEs, abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0
Maximum tolerated dose (dose escalation)
时间窗: Treatment + follow-up (estimated 9 months)
Number of participants with dose-limiting toxicity; incidence of adverse events (AEs), serious AEs (SAEs), abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0
Recommended Phase 2 doses (dose escalation)
时间窗: Treatment + follow-up (estimated 9 months)
Incidence of AEs, SAEs, abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0
Safety/tolerability - incidence of AEs, SAEs, abnormal laboratory parameters (dose escalation + expansion)
时间窗: Treatment + follow-up (estimated 21 months)
AEs, SAEs, abnormal laboratory parameters by type, severity, and relatedness as assessed by CTCAE v6.0
Safety/tolerability - incidence of TD001 discontinuation or modification due to AEs (dose escalation + expansion)
时间窗: Treatment + follow-up (estimated 21 months)
AEs by type, severity, and relatedness as assessed by CTCAE v6.0
次要结局
- Plasma PK - Ctrough(Estimated 6-8 months)
- PSA50 response rate(Treatment (estimated 8 months))
- Overall response rate(Treatment (estimated 8 months))
- PSA progression-free survival(Treatment + follow-up (estimated 21 months))
- Overall survival(Treatment + follow-up (estimated 21 months))
- Immunogenicity - prevalance and incidence of ADAs(Treatment period + follow-up (estimated 9 months))
- Plasma PK - T1/2(Estimated 6-8 months)
- Plasma PK - Tmax(Estimated 6-8 months)
- Plasma PK - AUC(Estimated 6-8 months)
- Plasma PK - AUClast(Estimated 6-8 months)
- Plasma PK - AUCtau(Estimated 6-8 months)
- Plasma PK - Cmax(Estimated 6-8 months)
- Plasma PK - Tmax(Estimated 6-8 months)
- Plasma PK - T1/2(Estimated 6-8 months)
- Plasma PK - Ctrough(Estimated 6-8 months)
- PSA50 response rate(Treatment (estimated 8 months))
- Overall response rate(Treatment (estimated 8 months))
- PSA progression-free survival(Treatment + follow-up (estimated 21 months))
- Radiographic progression-free survival(Treatment + follow-up (estimated 21 months))
- Duration of response(Treatment + follow-up (estimated 21 months))
- Disease control rate(Treatment (estimated 8 months))
- Overall survival(Treatment + follow-up (estimated 21 months))
- Immunogenicity - prevalance and incidence of ADAs(Treatment period + follow-up (estimated 9 months))