Clinical trial NCT03547973: Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread
Official title: A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Urothelial Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2018-06-06
Enrollment: 827
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5, 6, and 7. Cohort 5 has been cancelled, effective December 2023.

Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: 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)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: ORR Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7)
timeFrame: First dose date up to last dose date plus 30 days (approximately 3 years)
measure: Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7)
timeFrame: First dose date up to last dose date plus 30 days (approximately 3 years)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Duration of Response (DOR)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Progression-Free Survival (PFS)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Overall Survival (OS)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohorts 3, 4, 5, and 6)
timeFrame: First dose date up to last dose date plus 30 days (approximately 3 years)
measure: Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohorts 3, 4, 5, and 6)
timeFrame: First dose date up to last dose date plus 30 days (approximately 3 years)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-North Campus
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, PA
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine, Simmons Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, Downtown
state: Kentucky
city: Brandywine
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: Oncology Hematology West PC dba Nebraska Cancer Specialists
state: Nebraska
city: Albuquerque
country: United States
facility: Precision Cancer Research / New Mexico Oncology & Hematology Consultants
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Drug Shipping Address: New York-Presbyterian Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Easton
country: United States
facility: St. Luke's Hosptial - Bethlehem Campus
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of Southern Carolina
state: South Carolina
city: Knoxville
country: United States
facility: Thompson Oncology Group - Knoxville West
state: Tennessee
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital, Houston Methodist Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Hospital (IP Shipping Address)
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
city: Besançon
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Hopital Saint Andre (CHU de Bordeaux)
city: Brest
country: France
facility: Centre Hospitalier Regional Universitaire Brest
city: Clermont Ferrand Cedex
country: France
facility: Centre Jean Perrin
city: La Roche sur Yon
country: France
facility: Centre Hospitalier Departmental (CHD) Vendee
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Marseille CEDEX 9
country: France
facility: Institut Paoli Calmettes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nîmes cedex
country: France
facility: Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau
city: Paris Cedex 15
country: France
facility: Hopital European Georges-Pompidou (HEGP)
city: Paris
country: France
facility: Groupement Hospitalier Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Cochin
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Rennes
country: France
facility: Centre Hospitalier Prive Saint-Gregoire
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: Hospitaux Universitaires de Strasbourg - Hopital Civil
city: Suresnes
country: France
facility: Hospital Foch
city: Toulouse Cedex 9
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre les Nancy
country: France
facility: Institut de Cancerologie de Lorraine
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Duisburg
country: Germany
facility: Urologicum Duisburg
city: Frankfurt
country: Germany
facility: Centrum fur Hamatologie und Onkologie Bethanien
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Klinik für Urologie
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Herne
country: Germany
facility: Marien Hospital Herne
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Koblenz
country: Germany
facility: Institut für Versorgungsforschung in der Onkologie
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik
city: Münster
country: Germany
facility: Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie
city: Regensburg
country: Germany
facility: Universitat Regensburg
city: Tübingen
country: Germany
facility: Universitatsklinikum Tubingen, Klinik fur Urologie
city: Athens
country: Greece
facility: Henry Dunant Hospital Center, 4th Oncology Department
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina, Oncology Department
city: Marousi
country: Greece
facility: Athens Medical Center, Oncology Department
city: Patra
country: Greece
facility: General Hospital of Patras Agios Andreas
city: Volos
country: Greece
facility: Anassa General Clinic, Oncology-Chemotherapy Department
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico IRCCS
city: Cremona
country: Italy
facility: ASST Cremona
city: Genoa
country: Italy
facility: Ospedale Policlinico San Martino IRCCS
city: Meldola
country: Italy
facility: Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carita
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS - Ospedale Busonera
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: Instituto Nazionale Tumori Regina Elena - IFO
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Temi
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona srl
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongbuk-Gu
country: Korea, Republic of
facility: Korea University - Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Wonju-si
country: Korea, Republic of
facility: Yonsei University - Wonju Severance Christian Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: CEIC Hospital Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Las Palmas
country: Spain
facility: Complejo Hospitalario Universitario Insular Materno Infantil
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puera de Hierro Majadahonda
city: Manresa
country: Spain
facility: Hospital Sant Joan de Deu
city: Orense
country: Spain
facility: Complejo Hospitalario de Ourense
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi
city: Diyarbakir
country: Turkey
facility: Dicle Universitesi Tip Fakultesi Hastanesi
city: Edrine
country: Turkey
facility: Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi
city: Izmir
country: Turkey
facility: Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant
city: Seyhan
country: Turkey
facility: Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: Northwood
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Tagawa ST, Balar AV, Petrylak DP, Kalebasty AR, Loriot Y, Flechon A, Jain RK, Agarwal N, Bupathi M, Barthelemy P, Beuzeboc P, Palmbos P, Kyriakopoulos CE, Pouessel D, Sternberg CN, Hong Q, Goswami T, Itri LM, Grivas P. TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. J Clin Oncol. 2021 Aug 1;39(22):2474-2485. doi: 10.1200/JCO.20.03489. Epub 2021 Apr 30.