Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread

Metastatic Urothelial Cancer Clinical Trial

— TROPHY U-01  

Official title:

A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03547973
• Other study ID #: IMMU-132-06
• Secondary ID: 2018-001167-2320
• Status: Recruiting
• Phase: Phase 2
• Start date: August 13, 2018
• Est. completion date: July 2026

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: Gilead Clinical Study Information Center
• Phone: 1-833-445-3230 (GILEAD-0)
• Email: GileadClinicalTrials[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Description:

Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5 and 6. Cohort 5 has been cancelled, effective December 2023.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 643
• Est. completion date: July 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Female or male individuals, = 18 years of age (19 Years old for South Korea).

• Individuals with histologically confirmed urothelial cancer (UC).

• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.

• Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):

• Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;

• 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

• Adequate renal and hepatic function.

• Adequate hematologic parameters without transfusional support.

• Individuals must have a 3-month life expectancy.

Key Exclusion Criteria:

• 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 had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (ie, =Grade 1 from AEs due to a previously administered agent).

• 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.

• Requires concomitant medication interfering with UGT1A1 with no alternate option available.

• Has an active second malignancy.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Has known active Hepatitis B or Hepatitis C.

• Has other concurrent medical or psychiatric conditions.

• Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.

• Cohorts 3 to 5: 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Metastatic Urothelial Cancer

Intervention

Drug:
• Sacituzumab Govitecan-hziy
Administered intravenously.
• Pembrolizumab
Administered per package insert
• Cisplatin
Administered per package insert
• Avelumab
Administered per package insert
• Zimberelimab
Administered intravenously
• Carboplatin
Administered per package insert
• Gemcitabine
Administered per package insert
• Domvanalimab
Administered intravenously

Locations

Country	Name	City	State
France	Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz	Besançon
France	Hopital Saint Andre (CHU de Bordeaux)	Bordeaux
France	Centre Hospitalier Regional Universitaire Brest	Brest
France	Centre Jean Perrin	Clermont Ferrand Cedex
France	Centre Hospitalier Departmental (CHD) Vendee	La Roche sur Yon
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon Cedex 08
France	Institut Paoli Calmettes	Marseille CEDEX 9
France	Centre Antoine Lacassagne	Nice
France	Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau	Nîmes cedex
France	Groupement Hospitalier Pitie-Salpetriere	Paris
France	Hopital Cochin	Paris
France	Hopital European Georges-Pompidou (HEGP)	Paris Cedex 15
France	Centre Hospitalier Prive Saint-Gregoire	Rennes
France	Centre Eugene Marquis	Rennes Cedex
France	CHU de Rouen	Rouen
France	Hospitaux Universitaires de Strasbourg - Hopital Civil	Strasbourg
France	Hospital Foch	Suresnes
France	Institut Claudius Regaud	Toulouse Cedex 9
France	Institut de Cancerologie de Lorraine	Vandoeuvre les Nancy
France	Institut Gustave Roussy	Villejuif
Germany	Urologicum Duisburg	Duisburg
Germany	Centrum fur Hamatologie und Onkologie Bethanien	Frankfurt
Germany	Universitätsklinikum Frankfurt, Klinik für Urologie	Frankfurt
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Universitatsklinikum Hamburg-Eppendorf	Hamburg
Germany	University Hospital Heidelberg	Heidelberg
Germany	Marien Hospital Herne	Herne
Germany	Universitatsklinikum Jena	Jena
Germany	Institut für Versorgungsforschung in der Onkologie	Koblenz
Germany	Universitätsklinikum Magdeburg	Magdeburg
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Mainz
Germany	Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik	München
Germany	Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie	Münster
Germany	Universitat Regensburg	Regensburg
Germany	Universitatsklinikum Tubingen, Klinik fur Urologie	Tübingen
Greece	Henry Dunant Hospital Center, 4th Oncology Department	Athens
Greece	University General Hospital of Ioannina, Oncology Department	Ioannina
Greece	Athens Medical Center, Oncology Department	Marousi
Greece	General Hospital of Patras Agios Andreas	Patra
Greece	Anassa General Clinic, Oncology-Chemotherapy Department	Volos
Italy	Ospedale San Donato	Arezzo
Italy	Centro di Riferimento Oncologico IRCCS	Aviano
Italy	ASST Cremona	Cremona
Italy	Ospedale Policlinico San Martino IRCCS	Genoa
Italy	Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"	Meldola
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliero Universitaria Maggiore della Carita	Novara
Italy	Istituto Oncologico Veneto IRCCS - Ospedale Busonera	Padova
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Instituto Nazionale Tumori Regina Elena - IFO	Roma
Italy	Azienda Ospedaliera Santa Maria di Temi	Terni
Italy	Centro Ricerche Cliniche di Verona srl	Verona
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Korea University - Anam Hospital	Seongbuk-Gu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si
Korea, Republic of	Yonsei University - Wonju Severance Christian Hospital	Wonju-si
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Spain	Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol	Badalona
Spain	CEIC Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Complejo Hospitalario Universitario Insular Materno Infantil	Las Palmas
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Universitario Puera de Hierro Majadahonda	Majadahonda
Spain	Hospital Sant Joan de Deu	Manresa
Spain	Complejo Hospitalario de Ourense	Orense
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Turkey	Ankara Sehir Hastanesi	Ankara
Turkey	Dicle Universitesi Tip Fakultesi Hastanesi	Diyarbakir
Turkey	Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi	Edrine
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi	Istanbul
Turkey	Medipol Mega Universite Hastanesi	Istanbul
Turkey	T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant	Izmir
Turkey	Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi	Seyhan
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Barts Health NHS Trust	London
United Kingdom	East and North Hertfordshire NHS Trust	Northwood
United Kingdom	The Royal Marsden NHS Foundation Trust	Surrey
United States	Precision Cancer Research / New Mexico Oncology & Hematology Consultants	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Maryland Oncology Hematology, P.A.	Brandywine	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of Southern Carolina	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	St. Luke's Hosptial - Bethlehem Campus	Easton	Pennsylvania
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Houston Methodist Hospital, Houston Methodist Cancer Center	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Thompson Oncology Group - Knoxville West	Knoxville	Tennessee
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute, Downtown	Louisville	Kentucky
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Drug Shipping Address: New York-Presbyterian Hospital	New York	New York
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Woodlands Medical Specialists, PA	Pensacola	Florida
United States	Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Roanoke	Virginia
United States	University of Utah - Huntsman Cancer Hospital (IP Shipping Address)	Salt Lake City	Utah
United States	Mays Cancer Center	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Southern Illinois University School of Medicine, Simmons Cancer Institute	Springfield	Illinois
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Renovatio Clinical	The Woodlands	Texas
United States	The University of Arizona Cancer Center-North Campus	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria (Cohorts 1 to 4 and 6)	ORR will be defined as the rate of the best overall response as Complete Remission (CR) or Partial Response (PR) and based on central review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Primary	Progression free survival (PFS) based on central review by RECIST 1.1 criteria (Cohort 5 only)	PFS will be defined as the time from first dose until objective tumor progression, as assessed based on central review, or death, whichever comes first.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Overall Response Rate (ORR)	ORR will be defined as the rate of the best overall response as CR or PR and based on investigator review by RECIST 1.1 criteria for cohorts 3, 4, and 5. ORR will also be evaluated based on investigator review by Modified RECIST 1.1 for Immune-Based Therapeutics (iRECIST 1.1) for Cohort 3 only.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Duration of Response (DOR)	DOR will be calculated from the date of the first evaluation showing documented response, PR, or CR, to the date of the first disease progression or death and based on central and investigator review by RECIST 1.1 criteria for all cohorts. DOR will also be evaluated based on investigator review by iRECIST 1.1 for Cohort 3 only.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from the first dose until objective tumor progression,or death, whichever comes first and based on central and investigator review by RECIST 1.1 criteria for all cohorts. PFS will also be evaluated based on investigator review by iRECIST 1.1 for Cohort 3 only.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Overall Survival (OS)	OS will be measured from the date of first dose to death from any cause.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as CR + PR + Stable Disease (SD) for at least 6 months and based on central and investigator review by RECIST 1.1 criteria for cohorts 3, 4, and 5. CBR will also be evaluated based on investigator review by iRECIST 1.1 for Cohort 3 only.	Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Secondary	Cohorts 3, 4, and 5: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)		First dose date up to last dose date plus 30 days (approximately 3 years)
Secondary	Cohorts 3, 4, and 5: Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities		First dose date up to last dose date plus 30 days (approximately 3 years)

External Links

•   Gilead Clinical Trials Website