Study Details

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Metastatic Urothelial Cancer

Gender

N/A

Date

August 2018 - June 2030

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

Sacituzumab Govitecan-hziy, Pembrolizumab, Cisplatin, Avelumab, Zimberelimab, Carboplatin, Gemcitabine, Domvanalimab, Enfortumab Vedotin

Eligibility Information

Inclusion Criteria

Inclusion Criteria for All Cohorts:
Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
Adequate renal and hepatic function.
Adequate hematologic parameters without transfusional support.
Individuals must have a 3-month life expectancy.
Additional Inclusion Criteria for Cohorts 1 to 6:
Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
2. Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).
Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.
No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified
Additional Inclusion Criteria for Cohort 7:
No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is > 12 months since the last dose of systemic therapy.
Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Exclusion Criteria

Exclusion Criteria for All cohorts:
Females who are pregnant or lactating.
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Has an active second malignancy.
Has known active Hepatitis B or Hepatitis C.
Has other concurrent medical or psychiatric conditions.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has an active second malignancy.
Additional Exclusion Criteria for Cohorts 1 to 6:
For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade << 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.
Additional Exclusion Criteria for Cohort 7:
Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product.
Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
Have a Child-Pugh score of B or C.
Individuals with uncontrolled diabetes.
Have active keratitis or corneal ulcerations.
Participants with ongoing sensory or motor neuropathy Grade ≥ 2.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations

Locations (135)

The University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States, 85719

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

University of California San Francisco

San Francisco, California, United States, 94158

Rocky Mountain Cancer Centers

Littleton, Colorado, United States, 80120

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States, 06510

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, United States, 06360

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States, 33140

Woodlands Medical Specialists, PA

Pensacola, Florida, United States, 32503

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States, 30322

University of Illinois Cancer Center

Chicago, Illinois, United States, 60612

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

Southern Illinois University School of Medicine, Simmons Cancer Institute

Springfield, Illinois, United States, 62702

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202

Norton Cancer Institute, Downtown

Louisville, Kentucky, United States, 40202

Maryland Oncology Hematology, P.A.

Brandywine, Maryland, United States, 20613

University of Michigan

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Oncology Hematology West PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States, 68130

Precision Cancer Research / New Mexico Oncology & Hematology Consultants

Albuquerque, New Mexico, United States, 87109

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States, 10016

Drug Shipping Address: New York-Presbyterian Hospital

New York, New York, United States, 10065

Stony Brook Cancer Center

Stony Brook, New York, United States, 11794

St. Luke's Hosptial - Bethlehem Campus

Easton, Pennsylvania, United States, 18045

Medical University of Southern Carolina

Charleston, South Carolina, United States, 29425

Thompson Oncology Group - Knoxville West

Knoxville, Tennessee, United States, 37932

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States, 37232

Houston Methodist Hospital, Houston Methodist Cancer Center

Houston, Texas, United States, 77030

Mays Cancer Center

San Antonio, Texas, United States, 78229

Renovatio Clinical

The Woodlands, Texas, United States, 77380

University of Utah - Huntsman Cancer Hospital (IP Shipping Address)

Salt Lake City, Utah, United States, 84112

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22903

Virginia Oncology Associates

Hampton, Virginia, United States, 23666

Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

Roanoke, Virginia, United States, 24014

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States, 53705

Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz

Besançon, France, 25000

Hopital Saint Andre (CHU de Bordeaux)

Bordeaux, France, 33000

Centre Hospitalier Regional Universitaire Brest

Brest, France, 29200

Centre Jean Perrin

Clermont-Ferrand, France, 63011

Centre Hospitalier Departmental (CHD) Vendee

La Roche-sur-Yon, France, 85925

Centre Oscar Lambret

Lille, France, 59000

Centre Leon Berard

Lyon, France, 69373

Institut Paoli Calmettes

Marseille, France, 13273

Centre Antoine Lacassagne

Nice, France, 06189

Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau

Nîmes, France, 30029

Hopital European Georges-Pompidou (HEGP)

Paris, France, 33000

Groupement Hospitalier Pitie-Salpetriere

Paris, France, 75013

Hopital Cochin

Paris, France, 75014

Centre Hospitalier Prive Saint-Gregoire

Rennes, France, 35000

Centre Eugene Marquis

Rennes, France, 35042

CHU de Rouen

Rouen, France, 76031

Hospitaux Universitaires de Strasbourg - Hopital Civil

Strasbourg, France, 67200

Hospital Foch

Suresnes, France, 92150

Institut Claudius Regaud

Toulouse, France, 31059

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, France, 54519

Institut Gustave Roussy

Villejuif, France, 94800

Urologicum Duisburg

Duisburg, Germany, 47179

Centrum fur Hamatologie und Onkologie Bethanien

Frankfurt, Germany, 60389

Universitätsklinikum Frankfurt, Klinik für Urologie

Frankfurt, Germany, 60590

Universitatsklinikum Freiburg

Freiburg im Breisgau, Germany, 79106

Universitatsklinikum Hamburg-Eppendorf

Hamburg, Germany, 20246

University Hospital Heidelberg

Heidelberg, Germany, 69120

Marien Hospital Herne

Herne, Germany, 44625

Universitatsklinikum Jena

Jena, Germany, 07743

Institut für Versorgungsforschung in der Onkologie

Koblenz, Germany, 56068

Universitätsklinikum Magdeburg

Magdeburg, Germany, 39120

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Mainz, Germany, 55131

Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik

München, Germany, 81675

Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie

Münster, Germany, 48149

Universitat Regensburg

Regensburg, Germany, 93053

Universitatsklinikum Tubingen, Klinik fur Urologie

Tübingen, Germany, 72076

Henry Dunant Hospital Center, 4th Oncology Department

Athens, Greece, 11526

University General Hospital of Ioannina, Oncology Department

Ioannina, Greece, 45500

Athens Medical Center, Oncology Department

Marousi, Greece, 15125

General Hospital of Patras Agios Andreas

Pátrai, Greece, 26335

Anassa General Clinic, Oncology-Chemotherapy Department

Volos, Greece, 38333

Ospedale San Donato

Arezzo, Italy, 52100

Centro di Riferimento Oncologico IRCCS

Aviano, Italy, 33081

ASST Cremona

Cremona, Italy, 26100

Ospedale Policlinico San Martino IRCCS

Genoa, Italy, 16132

Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"

Meldola, Italy, 47014

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, 20133

IRCCS Ospedale San Raffaele

Milan, Italy, 20133

Azienda Ospedaliero Universitaria Maggiore della Carita

Novara, Italy, 28100

Istituto Oncologico Veneto IRCCS - Ospedale Busonera

Padua, Italy, 35128

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy, 56126

Instituto Nazionale Tumori Regina Elena - IFO

Roma, Italy, 00144

Azienda Ospedaliera Santa Maria di Temi

Terni, Italy, 05100

Centro Ricerche Cliniche di Verona srl

Verona, Italy, 37126

Kyungpook National University Chilgok Hospital

Daegu, South Korea, 41404

Keimyung University Dongsan Hospital

Daegu, South Korea, 42601

National Cancer Center

Goyang-si, South Korea, 10408

Chonnam National University Hospital

Gwangju, South Korea, 61469

Chonnam National University Hwasun Hospital

Hwasun, South Korea, 519-763

Korea University - Anam Hospital

Seongbuk-Gu, South Korea

Seoul National University Hospital

Seoul, South Korea, 03080

Yonsei University Health System, Severance Hospital

Seoul, South Korea, 03722

Samsung Medical Center

Seoul, South Korea, 06351

SMG-SNU Boramae Medical Center

Seoul, South Korea, 07061

Asan Medical Center

Seoul, South Korea, 5505

The Catholic University of Korea, St. Vincent's Hospital

Suwon, South Korea, 16247

Yonsei University - Wonju Severance Christian Hospital

Wŏnju, South Korea, 26426

Pusan National University Yangsan Hospital

Yangsan, South Korea, 50612

Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Spain, 08916

Hospital del Mar

Barcelona, Spain, 08003

Hospital Clinic de Barcelona

Barcelona, Spain, 08023

CEIC Hospital Vall d'Hebron

Barcelona, Spain, 08035

Hospital Universitario Reina Sofia

Córdoba, Spain, 14004

Complejo Hospitalario Universitario Insular Materno Infantil

Las Palmas, Spain, 35016

MD Anderson Cancer Centre

Madrid, Spain, 28033

Hospital Universitario Ramon Y Cajal

Madrid, Spain, 28034

Hospital Universitario Clinico San Carlos

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario Puera de Hierro Majadahonda

Majadahonda, Spain, 28222

Hospital Sant Joan de Deu

Manresa, Spain, 08243

Complejo Hospitalario de Ourense

Ourense, Spain, 32005

Hospital Universitario Marques de Valdecilla

Santander, Spain, 39008

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain, 15706

Hospital Clinico Universitario de Valencia

Valencia, Spain, 46010

Hospital Universitario Miguel Servet

Zaragoza, Spain, 50009

Ankara Sehir Hastanesi

Ankara, Turkey (Türkiye), 06550

Dicle Universitesi Tip Fakultesi Hastanesi

Diyarbakır, Turkey (Türkiye), 21280

Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi

Edrine, Turkey (Türkiye), 22030

Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi

Istanbul, Turkey (Türkiye), 34098

Medipol Mega Universite Hastanesi

Istanbul, Turkey (Türkiye), 34214

T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, Turkey (Türkiye), 34722

Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant

Izmir, Turkey (Türkiye), 35575

Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi

Seyhan, Turkey (Türkiye), 01250

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B9 5SS

Barts Health NHS Trust

London, United Kingdom, E1 1BB

East and North Hertfordshire NHS Trust

Northwood, United Kingdom, HA6 2JW

The Royal Marsden NHS Foundation Trust

Surrey, United Kingdom, SM2 5PT

Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (TROPHY U-01)

OVERVIEW

PROTOCOL SUMMARY