A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031) (TroFuse-031)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Paclitaxel; Biological: Sacituzumab tirumotecan; Drug: Rescue medications for sacituzumab tirumotecan; Drug: Vinflunine; Drug: Rescue medications for chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 590
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1419AHN
      • Recruiting
      • Asociacion de Beneficencia Hospital Sirio Libanes ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 01145744343
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Recruiting
      • Instituto Alexander Fleming ( Site 0002)
      • Contact: Study Coordinator; Phone Number: +541132218900
• Australia
  • New South Wales
    • Macquarie, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University ( Site 0031)
      • Contact: Study Coordinator; Phone Number: +61298505721
• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • AZ Maria Middelares ( Site 0063)
      • Contact: Study Coordinator; Phone Number: +3292469522
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • UZ Gent ( Site 0064)
      • Contact: Study Coordinator; Phone Number: +32 9 332 57 93
• Brazil
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Recruiting
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0110)
      • Contact: Study Coordinator; Phone Number: +551732015000
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Recruiting
      • Peking University First Hospital ( Site 0184)
      • Contact: Study Coordinator; Phone Number: 010-83572211
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center ( Site 0183)
      • Contact: Study Coordinator; Phone Number: +8602087343533
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center ( Site 0188)
      • Contact: Study Coordinator; Phone Number: +8602087343533
    • Guangzhou, Guangdong, China, 510280
      • Recruiting
      • Zhujiang Hospital of Southern Medical University ( Site 0205)
      • Contact: Study Coordinator; Phone Number: 020-61643888
    • Zhuhai, Guangdong, China, 519000
      • Recruiting
      • The Fifth Affiliated Hospital of Sun Yat-Sen University ( Site 0900)
      • Contact: Study Coordinator; Phone Number: 0756-25286878
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0198)
      • Contact: Study Coordinator; Phone Number: 027-85726685
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center ( Site 0181)
      • Contact: Study Coordinator; Phone Number: 021-64175590
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital Fudan University ( Site 0907)
      • Contact: Study Coordinator; Phone Number: 02164041990
  • Zhejiang
    • Ningbo, Zhejiang, China, 315201
      • Recruiting
      • The First Affiliated Hospital of Ningbo University ( Site 0193)
      • Contact: Study Coordinator; Phone Number: 0574-87075577
    • Wenzhou, Zhejiang, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School ( Site 0186)
      • Contact: Study Coordinator; Phone Number: 025-83106666
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University ( Site 0194)
      • Contact: Study Coordinator; Phone Number: +8613738301029
• Greece
  • Attica
    • Athens, Attica, Greece, 145 64
      • Recruiting
      • General Oncology Hospital of Kifisia "Agioi Anargyroi" ( Site 0335)
      • Contact: Study Coordinator; Phone Number: +302103501317
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus ( Site 0362)
    • Contact: Study Coordinator; Phone Number: 04-7776234
  • Jerusalem, Israel, 9103102
    • Recruiting
    • Shaare Zedek Medical Center ( Site 0366)
    • Contact: Study Coordinator; Phone Number: +97226555999
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center ( Site 0364)
    • Contact: Study Coordinator; Phone Number: 972-3-9378074
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 0361)
    • Contact: Study Coordinator; Phone Number: +97235303030
  • Ẕerifin, Israel, 7033001
    • Recruiting
    • Yitzhak Shamir Medical Center. ( Site 0367)
    • Contact: Study Coordinator; Phone Number: 972-8-9542196
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0396)
    • Contact: Study Coordinator; Phone Number: +39 02 2390 1
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Recruiting
      • Centro Ricerche Cliniche di Verona ( Site 0393)
      • Contact: Study Coordinator; Phone Number: +39 045 8126509
• Japan
  • Kagawa-ken
    • Kita-gun, Kagawa-ken, Japan, 761-0793
      • Recruiting
      • Kagawa University Hospital ( Site 0424)
      • Contact: Study Coordinator; Phone Number: +81-87-898-5111
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • Recruiting
      • St. Marianna University Hospital ( Site 0422)
      • Contact: Study Coordinator; Phone Number: +81-44-977-8111
  • Osaka
    • Sakai, Osaka, Japan, 591-8025
      • Recruiting
      • Osaka Rosai Hospital ( Site 0428)
      • Contact: Study Coordinator; Phone Number: +81-72-252-3561
  • Tokyo
    • Bunkyo, Tokyo, Japan, 113-8519
      • Recruiting
      • Institute of Science Tokyo Hospital ( Site 0421)
      • Contact: Study Coordinator; Phone Number: +81-33-813-6111
• Netherlands
  • Overijssel
    • Zwolle, Overijssel, Netherlands, 8025 AB
      • Recruiting
      • Isala, locatie Zwolle ( Site 0486)
      • Contact: Study Coordinator; Phone Number: +31886247573
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron ( Site 0607)
    • Contact: Study Coordinator; Phone Number: +34934893000
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos ( Site 0608)
    • Contact: Study Coordinator; Phone Number: 913303000
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre ( Site 0602)
    • Contact: Study Coordinator; Phone Number: +34 913 908 307
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Virgen del Rocio ( Site 0601)
    • Contact: Study Coordinator; Phone Number: +34 95 501 30 68
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • H. de Badalona Germans Trias I Pujol ( Site 0603)
      • Contact: Study Coordinator; Phone Number: 93 497 89 25
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Hospital Universitario Marques de Valdecilla ( Site 0605)
      • Contact: Study Coordinator; Phone Number: +34 942 20 25 25
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
      • Recruiting
      • Hospital Universitario Insular de Gran Canaria ( Site 0604)
      • Contact: Study Coordinator; Phone Number: +34 92 844 17 38
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28034
      • Recruiting
      • Hospital Universitario Ramon y Cajal ( Site 0606)
      • Contact: Study Coordinator; Phone Number: +34913368263
• Sweden
  • Stockholm County
    • Stockholm, Stockholm County, Sweden, 171 76
      • Recruiting
      • Karolinska Universitetssjukhuset Solna ( Site 0631)
      • Contact: Study Coordinator; Phone Number: +46812370000
• United States
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Recruiting
      • Munson Medical Center ( Site 0812)
      • Contact: Study Coordinator; Phone Number: 231-392-8400
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Recruiting
      • TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0822)
      • Contact: Study Coordinator; Phone Number: 513-865-5249
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Recruiting
      • Thompson Cancer Survival Center ( Site 0803)
      • Contact: Study Coordinator; Phone Number: 865-331-1720

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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 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

Exclusion Criteria:

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) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab tirumotecan; Participants receive 4 mg/kg of sacituzumab tirumotecan every 2 weeks (Q2W) via intravenous (IV) infusion until disease progression or unacceptable toxicity.	Biological: Sacituzumab tirumotecan; IV infusion; Other Names: SKB264; MK-2870; sac-TMT; Drug: Rescue medications for sacituzumab tirumotecan; Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are pegfilgrastim or equivalent, histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent, and steroid mouthwash (dexamethasone or equivalent).
Active Comparator: 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.	Drug: Docetaxel; IV infusion; Drug: Paclitaxel; IV infusion; Drug: Vinflunine; IV infusion; Drug: Rescue medications for chemotherapy; Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are dexamethasone or equivalent, H1 receptor antagonist, H2 receptor antagonist, and laxative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as time from randomization to death due to any cause.	Up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented.	Up to approximately 32 months
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.	Up to approximately 32 months
Duration of Response (DOR)	For participants who demonstrate a confirmed CR or PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented.	Up to approximately 49 months
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.	Up to approximately 49 months
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported.	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	EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score will be presented.	Baseline, up to approximately 49 months
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score will be presented.	Baseline, up to approximately 49 months
Change From Baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 2 questions about their role functioning (Items 6 and 7) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 6 and 7 is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. Per protocol, the change from baseline in the EORTC QLQ-C30 role functioning (items 6 and 7) combined score will be presented.	Baseline, up to approximately 49 months
Change From Baseline in EORTC QLQ-C30 Fatigue (Items 10, 12, and 18) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 3 questions about their fatigue (Items 10, 12, and 18) are scored on a 4-point scale (1 = Not at All to 4 = Very Much). The combined score of items 10, 12, and 18 is computed by averaging the raw scores of the 3 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A lower score indicates a better outcome. Per protocol, the change from baseline in the EORTC QLQ-C30 fatigue (items 10, 12, and 18) combined score will be presented.	Baseline, up to approximately 49 months
Change From Baseline in EORTC QLQ-C30 Nausea/Vomiting (Items 14 and 15) Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 2 questions about their nausea and vomiting symptoms (Items 14 and 15) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 14 and 15 is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A lower score indicates a better outcome. Per protocol, the change from baseline in the EORTC QLQ-C30 nausea/vomiting (Items 14 and 15) combined score will be presented.	Baseline, up to approximately 49 months
Change From Baseline in EORTC QLQ-C30 Diarrhea (Item 17) Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question: "Have you had diarrhea?" (Item 17) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. Per protocol, the change from baseline in the EORTC QLQ-C30 diarrhea (Item 17) score will be presented.	Baseline, up to approximately 49 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2026
• Primary Completion (Estimated): July 27, 2029
• Study Completion (Estimated): April 23, 2030

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Organic Chemicals; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Paclitaxel; Drug Therapy; vinflunine
• Other Study ID Numbers: 2870-031; U1111-1316-4390 (Registry Identifier: UTN); 2024-520014-22-00 (Registry Identifier: EU CT); MK-2870-031 (Other Identifier: MSD); jRCT2051260020 (Registry Identifier: Japan Registry of Clinical Trial (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No