A Phase 3, Randomized, Open-label Study of Sacituzumab Tirumotecan (MK-2870) Versus Investigator's Choice of Non-platinum Chemotherapy in Participants With Pretreated Locally Advanced/Metastatic Urothelial Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 590
- 试验地点
- 94
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
Researchers are looking for new ways to treat locally advanced or metastatic urothelial cancer (UC). Current treatments for locally advanced or metastatic UC include chemotherapy, immunotherapy, and targeted therapy.
Researchers want to know if giving sacituzumab tirumotecan (sac-TMT), the trial medicine, can treat locally advanced or metastatic UC that got worse after certain treatments. The goal of this trial is to learn if people who receive sac-TMT live longer than those who receive certain non-platinum chemotherapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •The main inclusion criteria include but are not limited to the following:
- •Has histologically documented locally advanced/metastatic urothelial cancer. Locally advanced disease must not be amenable to resection or radiation with curative intent per investigator assessment
- •Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the investigator
- •Has received treatment with anti-programmed cell death [ligand] 1 (anti-PD-[L]1) therapy, platinum-based chemotherapy, and enfortumab vedotin (EV)
- •Prior therapy with disitamab vedotin (DV) is allowed but will not meet the requirement for prior treatment with EV, except in China, where participants may have received DV instead of EV before study entry
- •Has received a maximum of 2 prior lines of therapy
- •Has experienced radiographic disease progression on or after the immediate prior line of therapy before study entry
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
- •Is eligible to receive at least one of the control arm nonplatinum chemotherapy options (paclitaxel, docetaxel, or vinflunine)
- •Is able to provide archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated
- •If human immunodeficiency virus (HIV) positive, has well-controlled HIV on antiretroviral therapy (ART)
- •If hepatitis B surface antigen (HBsAg) positive, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load
- •If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load
- •Has adequate organ function
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from adverse event (AE) associated with anticancer therapy
- •Has received prior therapy with trophoblast cell-surface antigen 2 (TROP2)-targeted antibody drug conjugate (ADC)
- •Has received prior therapy with a topoisomerase 1 inhibitor-containing ADC
- •Has completed prior external radiotherapy within 6 weeks or stereotactic radiotherapy within 4 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
- •Has received prior chemotherapy for urothelial cancer with any of the study therapies in the control arm (paclitaxel, docetaxel, and vinflunine)
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has a current or past history of central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active infection requiring systemic therapy other than those permitted per protocol
- •Has a history of stem cell/solid organ transplant
- •Has not adequately recovered from major surgery, or has ongoing surgical complications
研究组 & 干预措施
Chemotherapy
Participants receive paclitaxel 175 mg/m^2, docetaxel 75 mg/m^2, or vinflunine 320 mg/m^2 IV every 3 weeks (Q3W), at the investigator's discretion, until disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg of sacituzumab tirumotecan every 2 weeks (Q2W) via intravenous (IV) infusion until disease progression or unacceptable toxicity.
干预措施: Rescue medications for sacituzumab tirumotecan (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg of sacituzumab tirumotecan every 2 weeks (Q2W) via intravenous (IV) infusion until disease progression or unacceptable toxicity.
干预措施: Sacituzumab tirumotecan (Biological)
Chemotherapy
Participants receive paclitaxel 175 mg/m^2, docetaxel 75 mg/m^2, or vinflunine 320 mg/m^2 IV every 3 weeks (Q3W), at the investigator's discretion, until disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Chemotherapy
Participants receive paclitaxel 175 mg/m^2, docetaxel 75 mg/m^2, or vinflunine 320 mg/m^2 IV every 3 weeks (Q3W), at the investigator's discretion, until disease progression or unacceptable toxicity.
干预措施: Vinflunine (Drug)
Chemotherapy
Participants receive paclitaxel 175 mg/m^2, docetaxel 75 mg/m^2, or vinflunine 320 mg/m^2 IV every 3 weeks (Q3W), at the investigator's discretion, until disease progression or unacceptable toxicity.
干预措施: Rescue medications for chemotherapy (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 40 months
OS is defined as time from randomization to death due to any cause.
次要结局
- Progression-Free Survival (PFS)(Up to approximately 32 months)
- Objective Response Rate (ORR)(Up to approximately 32 months)
- Duration of Response (DOR)(Up to approximately 49 months)
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 49 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 48 months)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score(Baseline, up to approximately 49 months)
- Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline, up to approximately 49 months)
- Change From Baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score(Baseline, up to approximately 49 months)
- Change From Baseline in EORTC QLQ-C30 Fatigue (Items 10, 12, and 18) Combined Score(Baseline, up to approximately 49 months)
- Change From Baseline in EORTC QLQ-C30 Nausea/Vomiting (Items 14 and 15) Combined Score(Baseline, up to approximately 49 months)
- Change From Baseline in EORTC QLQ-C30 Diarrhea (Item 17) Score(Baseline, up to approximately 49 months)