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

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

Status
Active, not recruiting
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03547973
Acronym
TROPHY U-01
Enrollment
502
Registered
2018-06-06
Start date
2018-08-13
Completion date
2030-04-01
Last updated
2026-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Urothelial Cancer

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.

Interventions

DRUGSacituzumab Govitecan-hziy

Administered intravenously.

DRUGPembrolizumab

Administered per package insert

DRUGCisplatin

Administered per package insert

DRUGAvelumab

Administered per package insert

DRUGZimberelimab

Administered intravenously

DRUGCarboplatin

Administered per package insert

DRUGGemcitabine

Administered per package insert

DRUGDomvanalimab

Administered intravenously

DRUGEnfortumab Vedotin

Administered intravenously

Sponsors

Gilead Sciences
Lead SponsorINDUSTRY
Merck KGaA, Darmstadt, Germany
CollaboratorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
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)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on central review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))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.
ORR Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on investigator review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7)First dose date up to last dose date plus 30 days (approximately 3 years)
Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7)First dose date up to last dose date plus 30 days (approximately 3 years)

Secondary

MeasureTime frameDescription
Overall Response Rate (ORR)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))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, 6, and 7. ORR will also be evaluated based on investigator review by Modified RECIST 1.1 for Immune-Based Therapeutics (iRECIST 1.1) for Cohorts 3, 4, 6, and 7.
Duration of Response (DOR)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))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 Cohorts 3, 4, 6, and 7.
Progression-Free Survival (PFS)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))PFS is defined as the time from the first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) 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 Cohorts 3, 4, 6, and 7.
Overall Survival (OS)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))OS will be measured from the date of first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) to death from any cause.
Clinical Benefit Rate (CBR)Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))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, 6, and 7. CBR will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohorts 3, 4, 5, and 6)First dose date up to last dose date plus 30 days (approximately 3 years)
Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohorts 3, 4, 5, and 6)First dose date up to last dose date plus 30 days (approximately 3 years)

Countries

France, Germany, Greece, Italy, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States

Contacts

STUDY_DIRECTORGilead Study Director

Gilead Sciences

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Sep 2, 2026