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

Official Summary

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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 590 participants

Study Arms

• Sacituzumab tirumotecan (EXPERIMENTAL)
  Participants receive 4 mg/kg of sacituzumab tirumotecan every 2 weeks (Q2W) via intravenous (IV) infusion until disease progression or unacceptable toxicity.
• Chemotherapy (ACTIVE_COMPARATOR)
  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.

Interventions

• BIOLOGICAL: Sacituzumab tirumotecan — IV infusion
• DRUG: Vinflunine — IV infusion
• DRUG: Docetaxel — IV infusion
• DRUG: Paclitaxel — IV infusion
• 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).

Primary Outcomes

• Overall Survival (OS) (Up to approximately 40 months)

Secondary Outcomes

• 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)

Eligibility Criteria

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

Trial Locations

• TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0822), Cincinnati, Ohio, United States
• Thompson Cancer Survival Center ( Site 0803), Knoxville, Tennessee, United States
• Asociacion de Beneficencia Hospital Sirio Libanes ( Site 0003), Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
• Instituto Alexander Fleming ( Site 0002), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
• Macquarie University ( Site 0031), Macquarie, New South Wales, Australia
• AZ Maria Middelares ( Site 0063), Ghent, Oost-Vlaanderen, Belgium
• UZ Gent ( Site 0064), Ghent, Oost-Vlaanderen, Belgium
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0110), São José do Rio Preto, São Paulo, Brazil
• Peking University First Hospital ( Site 0184), Beijing, Beijing Municipality, China
• Sun Yat-Sen University Cancer Center ( Site 0183), Guangzhou, Guangdong, China
• ...and 10 more locations

Contact Information

• Toll Free Number — CONTACT
  Phone: 1-888-577-8839
  Email: Trialsites@msd.com

Study Officials

• Medical Director — STUDY_DIRECTOR
  Merck Sharp & Dohme LLC

More Bladder Cancer Trials

View all Bladder Cancer clinical trials