Actively Recruiting
A Phase III Randomized Trial of Pembrolizumab and Sacituzumab Govitecan-hziy Versus Standard Chemotherapy in Advanced Urothelial Cancer
Led by National Cancer Institute (NCI) · Updated on 2026-06-02
320
Participants Needed
148
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of pembrolizumab and sacituzumab govitecan-hziy compared to standard chemotherapy treatments in patients with urothelial cancer that has spread locally or to other parts of the body. This phase III trial aims to assess overall survival, progression-free survival, response rates, clinical benefit, and treatment safety. The study also explores quality of life and fatigue changes during treatment to better understand patient experiences. Participants are randomly assigned to one of two groups. One group receives standard chemotherapy options such as carboplatin or cisplatin with gemcitabine, or alternatively docetaxel or paclitaxel, given intravenously in cycles every 21 days for up to six cycles. The other group receives pembrolizumab intravenously on day 1 and sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle, continuing for up to 35 cycles or two years, unless the disease progresses or toxicity occurs. Both groups undergo blood sample collection and imaging scans like CT or MRI throughout the study. During the study, participants will have regular visits for treatment administration, blood tests, and imaging to monitor disease status and treatment effects. Researchers will collect data on survival, tumor response, side effects, and quality of life using questionnaires at multiple time points up to five years from the start of treatment. After finishing treatment, patients are followed up 30 days later and then once a year for five years to track long-term outcomes and safety.
CONDITIONS
Brief Title
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitean-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient must be 18 years of age or older
- Patient must have an ECOG performance status of 0 to 2
- Patient must have locally advanced or metastatic urothelial cancer
- Patient must have histologically confirmed conventional urothelial carcinoma with at least 1% conventional urothelial histology
- Patient must have measurable disease per RECIST 1.1 criteria with baseline imaging within 35 days prior to randomization
- Patient must have had progression on or after prior anti-PD(L)1 therapy, having received at least one dose
- Patient must have received at least one line of systemic therapy in the advanced/metastatic setting or have progressed within 12 months after localized anti-PD(L)1 + enfortumab vedotin therapy
- Patients with FGFR3+ tumors must have received a prior FGFR inhibitor unless contraindicated
- Patient must have received prior enfortumab vedotin or other Nectin-4 directed therapy unless contraindicated
- Patient must not have prior exposure to sacituzumab govitecan-hziy or other TROP-2 directed antibody-drug conjugates
- Patient must have a Bellmunt score of 0 to 2
- Patient must not have had grade 3 or higher immune-related adverse events from prior anti-PD1/L1 except for controlled endocrinopathies
- Patient must have recovered from prior treatment-related adverse events to grade 1 or less except for certain neuropathies, alopecia, or non-clinically significant lab abnormalities
- Patient must not be pregnant or breastfeeding and must use effective contraception if of childbearing potential
- Patient must be able and willing to sign informed consent
- Patient must meet specific blood count and organ function criteria within 14 days prior to randomization
- Patient must not have known genetic UGT1A1 deficiency
- HIV-infected patients must be on effective therapy with undetectable viral load
- Patients with hepatitis B or C must meet specific viral load or treatment criteria
- Patients with treated brain metastases must show no progression and no high-dose steroid use
- Patient must not be on systemic immunosuppressive medication exceeding prednisone 10 mg daily
- Patient must be English or Spanish speaking for the quality of life study component
You will not qualify if you...
- Pure non-urothelial histology tumors
- Progression within 12 weeks of starting first anti-PD(L)1 therapy
- History of grade 3 or higher immune-related adverse events from prior anti-PD1/L1 except controlled endocrinopathies
- Unrecovered clinically significant adverse events from previous systemic therapy above grade 1 except certain exceptions
- Pregnancy or breastfeeding
- Known genetic UGT1A1 deficiency (Gilbert's syndrome)
- Active HIV infection without effective therapy or detectable viral load
- Active hepatitis B or C infection not meeting viral load or treatment criteria
- Untreated or progressing brain metastases or use of high-dose steroids for brain metastases
- Use of systemic immunosuppressive medication exceeding prednisone 10 mg daily at enrollment
- Non-English or non-Spanish speakers for quality of life component
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