Sacituzumab Tirumotecan vs MMAE-ADCs in Advanced Urothelial Carcinoma (FUSCC-SPARE-UC-01)

Starting soon · Phase 2

Conditions studied: Bladder Cancer, Metastatic Urothelial Carcinoma, Urothelial Carcinoma, Peripheral Neuropathy

In brief

The main goal of this clinical trial is to learn if a new targeted cancer drug called sacituzumab tirumotecan (sac-TMT) works to treat cancer while causing less nerve damage in patients with advanced urothelial carcinoma who have progressed on or could not tolerate previous treatment such as enfortumab vedotin plus pembrolizumab (EVP) or disitamab vedotin plus toripalimab (DVT). The main question it aims to answer is: Does sac-TMT lower the risk of getting severe nerve damage, as measured together by doctors, machines, and the participants? Researchers will compare sac-TMT to alternative MMAE-based ADC drugs (switching to a different MMAE-based ADC after the first one stopped working) to see if sac-TMT causes less nerve damage while still effectively treating the cancer. A small group of participants who had to stop their previous MMAE-based ADC treatment because of nerve damage will also receive sac-TMT to learn if the drug is safe for their nerves. Participants will: 1. Receive either sac-TMT or another MMAE-based ADC drug 2. Have regular physical exams by a doctor to check their nerves 3. Have machine tests to measure how well their nerves work 4. Answer survey questions about their pain, numbness, and daily activities

Key facts

Study ID

NCT07662863

Run by

Fudan University

People needed

75

Starts

2026-07-15

Expected to finish

2029-12-01

Last updated by the study team

2026-06-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Must voluntarily sign the written Institutional Review Board (IRB)/Ethics Committee (EC) approved informed consent form (ICF) prior to any screening procedures.
• Age > 18 years at the time of signing the ICF.
• Histologically or cytologically confirmed locally advanced (unresectable) or metastatic urothelial carcinoma (UC), including bladder, ureter, renal pelvis, or urethra. Participants with mixed histology are eligible provided that UC is the predominant component (> 50%).
• Must have received at least one prior line of systemic therapy for locally advanced or metastatic UC (e.g., Enfortumab Vedotin plus Pembrolizumab, Disitamab Vedotin plus Toripalimab, platinum-based chemotherapy, immune checkpoint inhibitors, Nectin-4 ADCs, HER2 ADCs, FGFR inhibitors, or other palliative chemotherapy regimens).
• Neuropathy Status:
• Cohort A/B: Baseline peripheral neuropathy (PN) Grade 0-1 (per NCI-CTCAE v5.0) with stable nerve function confirmed by Nerve Conduction Study (NCS) during screening.
• Cohort C (Observational): Baseline PN Grade 2, or a history of PN > Grade 2 where the investigator deems the patient unsuitable for MMAE-based ADC treatment.
• At least one measurable lesion per RECIST v1.1. (Lesions in previously irradiated areas are considered target lesions only if clear progression is documented after radiotherapy).
• ECOG Performance Status of 0 or 1 at screening.
• Expected survival > 3 months.
• Must have adequate organ and bone marrow function (no blood transfusion, growth factors, or albumin support within 14 days prior to screening):
• Hematological: ANC >= 1.5 x 10\^9/L; Platelets >= 75 x 10\^9/L; Hemoglobin >= 90 g/L.
• Hepatic: ALT and AST <= 2.5 x ULN (or <= 5 x ULN for patients with liver metastases); Total Bilirubin <= 1.5 x ULN (if Total Bilirubin > 1.5 x ULN, Direct Bilirubin must be <= ULN).
• Coagulation: INR <= 1.5; APTT <= 1.5 x ULN; PT < ULN + 4 seconds.
• Renal: Creatinine Clearance (CrCl) >= 30 mL/min, or Serum Creatinine <= 1.5 x ULN.

You may not qualify if…

• Prior treatment with TROP2-targeted ADCs, topoisomerase I inhibitors (e.g., irinotecan, topotecan), or ADCs containing topoisomerase I inhibitor payloads.
• Patients previously treated with both Enfortumab Vedotin (EV) and Disitamab Vedotin (DV) are excluded from Cohorts A and B (eligible for Cohort C only).
• Treatment with any investigational anti-tumor agents, chemotherapy, immunotherapy, monoclonal antibodies, targeted therapy, or radical radiotherapy within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose. Major surgery within 4 weeks prior to the first dose.
• Active CNS or meningeal metastases. Patients with previously treated CNS metastases are eligible if clinically stable for ≥ 4 weeks, off systemic corticosteroids for ≥ 2 weeks (physiological replacement ≤ 10 mg/day prednisone equivalent is allowed), and no evidence of radiographic progression.
• History of non-infectious pneumonitis/interstitial lung disease (ILD) requiring steroids. Current ILD or suspected ILD on screening chest CT (even if asymptomatic). Severe COPD, severely impaired lung function, or requirement for long-term oxygen therapy.
• QTcF interval > 470 ms (females) or > 450 ms (males). Within 6 months prior to the first dose: myocardial infarction, unstable angina, severe arrhythmia requiring intervention, uncontrolled hypertension, stroke, or TIA. NYHA Class III or IV congestive heart failure.
• Active keratitis, corneal ulcer, or severe dry eye syndrome.
• Active Hepatitis B (HBsAg positive and HBV-DNA > 2000 IU/mL; patients with lower HBV-DNA must receive antiviral therapy); Active Hepatitis C (HCV antibody and RNA positive); Known HIV infection; Severe infection requiring IV antibiotics within 2 weeks prior to first dose.
• Hypersensitivity: Known severe hypersensitivity to sac-TMT, EV, DV, or their excipients.
• Any severe or uncontrolled systemic disease that, in the investigator's opinion, increases the risk to the participant.
• HbA1c ≥ 8% (Patients with well-controlled blood glucose, fasting glucose ≤ 10 mmol/L, and investigator approval are eligible).
• History of allogeneic stem cell transplant or solid organ transplant.
• Pregnant or breastfeeding females.

Where it is running

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China

Full record on ClinicalTrials.gov

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