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

Official title

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

Overview

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.

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).
• 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.

Primary outcome measures

• Overall Survival (OS) [Time frame: Up to approximately 40 months]

Secondary outcome measures (11)

• Progression-Free Survival (PFS) [Time frame: Up to approximately 32 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 32 months]
• Duration of Response (DOR) [Time frame: Up to approximately 49 months]
• Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 49 months]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: 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 [Time frame: Baseline, up to approximately 49 months]
• Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score [Time frame: Baseline, up to approximately 49 months]
• Change From Baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score [Time frame: Baseline, up to approximately 49 months]
• Change From Baseline in EORTC QLQ-C30 Fatigue (Items 10, 12, and 18) Combined Score [Time frame: Baseline, up to approximately 49 months]
• Change From Baseline in EORTC QLQ-C30 Nausea/Vomiting (Items 14 and 15) Combined Score [Time frame: Baseline, up to approximately 49 months]
• Change From Baseline in EORTC QLQ-C30 Diarrhea (Item 17) Score [Time frame: Baseline, up to approximately 49 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 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

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) 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 14 centers

• Peking University First Hospital ( Site 0184) — Beijing
• The First Affiliated Hospital of Chonqing Medical University ( Site 0197) — Chongqing
• Sun Yat-Sen University Cancer Center ( Site 0183) — Guangzhou
• Sun Yat-Sen University Cancer Center ( Site 0188) — Guangzhou
• Zhujiang Hospital of Southern Medical University ( Site 0205) — Guangzhou
• The Fifth Affiliated Hospital of Sun Yat-Sen University ( Site 0900) — Zhuhai
• Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site — Wuhan
• Fudan University Shanghai Cancer Center ( Site 0181) — Shanghai
• … and 6 more centers

Japan · 12 centers

• Hokkaido University Hospital ( Site 0436) — Sapporo
• Kobe University Hospital ( Site 0431) — Kobe
• University of Tsukuba Hospital ( Site 0432) — Tsukuba
• Kagawa University Hospital ( Site 0424) — Kita-gun
• St. Marianna University Hospital ( Site 0422) — Kawasaki
• Kitasato University Hospital ( Site 0425) — Sagamihara
• Nara Medical University Hospital ( Site 0423) — Kashihara
• Osaka Rosai Hospital ( Site 0428) — Sakai
• … and 4 more centers

Spain · 8 centers

• H. de Badalona Germans Trias I Pujol ( Site 0603) — Badalona
• Hospital Universitario Marques de Valdecilla ( Site 0605) — Santander
• Hospital Universitario Insular de Gran Canaria ( Site 0604) — Las Palmas de Gran Canaria
• Hospital Universitario Ramon y Cajal ( Site 0606) — Madrid
• Hospital Universitari Vall d'Hebron ( Site 0607) — Barcelona
• Hospital Clinico San Carlos ( Site 0608) — Madrid
• Hospital Universitario 12 de Octubre ( Site 0602) — Madrid
• Hospital Virgen del Rocio ( Site 0601) — Seville

United States · 7 centers

• Munson Medical Center ( Site 0812) — Traverse City
• Memorial Sloan Kettering Cancer Center ( Site 0832) — New York
• WakeMed Raleigh Campus ( Site 0811) — Raleigh
• TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0822) — Cincinnati
• The West Clinic, P.C. ( Site 0791) — Germantown
• Thompson Cancer Survival Center ( Site 0803) — Knoxville
• Virginia Oncology Associates (VOA) ( Site 8002) — Norfolk

Italy · 6 centers

• Istituto Clinico Humanitas ( Site 0398) — Rozzano
• Centro Ricerche Cliniche di Verona ( Site 0393) — Verona
• Ospedale San Donato. Azienda Sanitaria Toscana Sud Est ( Site 0392) — Arezzo
• IRCCS Azienda Ospedaliera Metropolitana ( Site 0394) — Genova
• Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0396) — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Roma

Netherlands · 6 centers

• Maastricht UMC+ ( Site 0483) — Maastricht
• Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0482) — Amsterdam
• Elisabeth-TweeSteden Ziekenhuis ( Site 0489) — Tilburg
• Isala, locatie Zwolle ( Site 0486) — Zwolle
• Erasmus Medisch Centrum ( Site 0481) — Rotterdam
• St. Antonius Ziekenhuis, locatie Utrecht ( Site 0488) — Utrecht

Israel · 5 centers

• Rambam Health Care Campus ( Site 0362) — Haifa
• Shaare Zedek Medical Center ( Site 0366) — Jerusalem
• Rabin Medical Center ( Site 0364) — Petah Tikva
• Sheba Medical Center ( Site 0361) — Ramat Gan
• Yitzhak Shamir Medical Center. ( Site 0367) — Ẕerifin

Belgium · 4 centers

• Cliniques Universitaires Saint-Luc ( Site 0062) — Brussels
• AZ Maria Middelares ( Site 0063) — Ghent
• UZ Gent ( Site 0064) — Ghent
• CHC Montlegia Clinic ( Site 0061) — Liège

Greece · 4 centers

• General Oncology Hospital of Kifisia "Agioi Anargyroi" ( Site 0335) — Athens
• METROPOLITAN GENERAL HOSPITAL-ONCOLOGIC CLINICAL TRIALS AND RESEARCH CLINIC ( Site 0332) — Athens
• University General Hospital ''Attikon'' - General Hospital of West Attica "H AGIA VARVARA" — Chaïdári
• Athens Medical Center ( Site 0336) — Marousi

Argentina · 3 centers

• Asociacion de Beneficencia Hospital Sirio Libanes ( Site 0003) — Ciudad Autonoma de Buenos Aires
• Instituto Alexander Fleming ( Site 0002) — Ciudad Autónoma de Buenos Aires
• Instituto de Oncologia de Rosario ( Site 0005) — Rosario

Brazil · 3 centers

• ICTRIALS Pesquisa e Desenvolvimento ( Site 0107) — Curitiba
• Hospital Moinhos de Vento ( Site 0102) — Porto Alegre
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0110) — São José do Rio Preto

Australia · 2 centers

• Macquarie University ( Site 0031) — Macquarie
• Mater Hospital Brisbane ( Site 0032) — South Brisbane

Sweden · 2 centers

• Laenssjukhuset Ryhov ( Site 0632) — Jönköping
• Karolinska Universitetssjukhuset Solna ( Site 0631) — Stockholm

Canada · 1 center

• Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésu — Québec

France · 1 center

• CHRU de Brest ( Site 0272) — Brest

United Kingdom · 1 center

• Cambridge University Hospitals NHS Foundation Trust ( Site 0756) — Cambridge

Identifiers

NCT: NCT07419295 · 2870-031 · U1111-1316-4390 · 2024-520014-22-00 · MK-2870-031 · jRCT2051260020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗