A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan Versus Sacituzumab Govitecan Alone in the Treatment of Advanced Urothelial Cancer
NCT Number: NCT06524544
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Locally Advanced Urothelial Carcinoma|Metastatic Urothelial Carcinoma
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Computed Tomography|PROCEDURE: Magnetic Resonance Imaging|BIOLOGICAL: Pembrolizumab|OTHER: Questionnaire Administration|BIOLOGICAL: Sacituzumab Govitecan
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 384
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2025-02-06
Completion Date: 2028-12-31

Summary:
This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitecan to sacituzumab govitecan alone in treating patients with urothelial cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug called govitecan. Sacituzumab attaches to TROP2 positive tumor cells in a targeted way and delivers govitecan to kill them. Giving pembrolizumab and sacituzumab govitecan may be more effective than sacituzumab govitecan alone in treating patients with locally advanced or metastatic urothelial cancer.

Primary Outcome Measures: Overall survival (OS), OS will be characterized with the method of Kaplan-Meier and will be compared between the two treatment arms using stratified log-rank test. The hazard ratio (HR) will be estimated, and a 95% confidence interval (CI) will be reported., From randomization to death due to any cause, assessed up to 5 years
Secondary Outcome Measures: Progression-free survival (PFS), PFS will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PFS will be characterized with the method of Kaplan-Meier and will be compared between the two treatment arms using stratified log-rank test. The HR will be estimated, and a 95% CI will be reported., From randomization to the earlier progression or death due to any cause, assessed up to 5 years|Overall response rate (ORR), ORR will be assessed among patients who received at least one dose of protocol therapy using RECIST v 1.1 criteria. ORR will be defined as the number of patients with complete response (CR) and partial response (PR) divided by the number of treated patients. ORR will be calculated based on the definition by arm and will be reported with 95% CI., Up to 5 years|Clinical benefit rate (CBR), CBR will be defined as CR, PR, or stable disease per RECIST v 1.1. CBR will be calculated based on the definition by arm and will be reported with 95% CI., Up to 5 years|Duration of response (DOR), DOR will be assessed by RECIST v1.1. DOR will be characterized with the method of Kaplan-Meier and will be compared between the two treatment arms using stratified log-rank test. The HR will be estimated, and a 95% CI will be reported., From the first occurrence of a documented objective response to disease progression or death, whichever occurs first, assessed up to 5 years|Incidence of adverse events (AEs), AEs will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The percentage of patients with toxicities will be tabulated. The 90% CI for the true probability of observing toxicity of ≥ grade 4 on a given arm will be no wider than 12.3 %. The probability of observing ≥ 1 toxicity on a given arm with a true rate of 1% is 85.5%., Up to 30 days after last dose of study drug
Other Outcome Measures: Clinical outcomes (OS, PFS, ORR, CBR) based on prior checkpoint inhibitor therapy response primary, Will compare with clinical outcomes based on prior checkpoint inhibitor therapy response secondary resistance. The primary endpoint OS will also be analyzed by sex, race, and ethnicity. The corresponding 95% CIs will also be reported., Up to 5 years|Clinical outcomes (OS, PFS, ORR, CBR) based on secondary resistance, Will compare with clinical outcomes based on prior checkpoint inhibitor therapy response primary resistance. The primary endpoint OS will also be analyzed by sex, race, and ethnicity. The corresponding 95% CIs will also be reported., Up to 5 years|Clinical outcomes (OS, PFS, ORR, CBR) based on prior exposure to enfortumab vedotin, The primary endpoint OS will also be analyzed by sex, race, and ethnicity. The corresponding 95% CIs will also be reported., Up to 5 years|Clinical outcomes (OS, PFS, ORR, CBR) based on prior exposure to platinum-based chemotherapy (cisplatin/carboplatin), The primary endpoint OS will also be analyzed by sex, race, and ethnicity. The corresponding 95% CIs will also be reported., Up to 5 years|Clinical outcomes (OS, PFS, ORR, CBR) based on Bellmunt score/risk factors and the rate of continuation beyond progression, The primary endpoint OS will also be analyzed by sex, race, and ethnicity. The corresponding 95% CIs will also be reported., Up to 5 years|Change in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBISI-18) summary score, Change in patient reported FBISI-18 score will be compared between arms using a two-sample t-test. Assessment time will be considered as a continuous variable if there is a linear trend in quality of life (QOL) assessments over time or a set of dummy variables if a non-linear trend exists. Patient demographics and disease characteristics will be adjusted in the mixed effect model. A t-test will be performed to explore change of FBISI-18 summary score., At baseline and at 3, 6 and 12 months|Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) summary score, Change in patient reported FACIT-F score will be compared between arms using a two-sample t-test. Mixed effect models will be constructed to estimate the time profile of FACIT-F in the two arms and to evaluate treatment-by-time interactions. Assessment time will be considered as a continuous variable if there is a linear trend in QOL assessments over time or a set of dummy variables if a non-linear trend exists. Patient demographics and disease characteristics will be adjusted in the mixed effect model., At baseline and at 3, 6 and 12 months|Change in quality-adjusted survival (assessed by the European Quality of Life Five Dimension Five Level scale [EQ-5D-5L])., Change in patient reported EQ-5D-5L will be compared between the arms using a two-sample t-test. Quality-adjusted survival (assessed by the EQ-5D-5L), will be analyzed with quality-adjusted time without symptoms or toxicity., At baseline and at 3, 6 and 12 months