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
- 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 3 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
- 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) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- 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
18age old over
No limit
Both
Urothelial Carcinoma
- Arm 1: Sacituzumab tirumotecan 4 mg/kg q2w until disease progression or unacceptable
toxicity.
- Arm 2: Investigator's choice of paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine
320 mg/m2 q3w until disease progression or unacceptable toxicity.
Overall Survival (OS): The time from randomization to death due to any cause
- Progression-free survival (PFS): The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first
- Objective response: A confirmed partial response (PR) or complete response (CR)
- Duration of response (DOR): For participants with a confirmed response, the time from first documented evidence of CR or PR until either disease progression or death due to any cause, whichever occurs first
- Adverse events (AEs)
- Study intervention discontinuation due to AEs
- EORTC QLQ-C30 global health status/QoL (Items 29 and 30)
- EORTC QLQ-C30 physical functioning (Items 1-5)
- EORTC QLQ-C30 role functioning (Items 6 and 7)
- EORTC QLQ-C30 fatigue (Items 10, 12 and 18)
- EORTC QLQ-C30 nausea/vomiting (Items 14 and 15)
- EORTC QLQ-C30 diarrhea (Item 17)
MSD K.K.
Osaka Rosai Hospital Institutional Review Board
1179-3, Nagasone-cho, Kita-ku, Sakai-city, Osaka
+81-72-252-3561
Approval
Mar. 13, 2026
Yes
https://engagezone.msd.com/
NCT07419295
ClinicalTrials.gov
Argentina/Australia/Brazil/Canada/China/Israel/ the United Kingdom/United States of America/Belgium/France/Germany/Greece/Italy/Netherlands/Spain/Sweden
