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

NCT07662863 | Not Yet Recruiting Phase 2

• 1 other identifier: FUSCC-SPARE-UC-01
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Receive either sac-TMT or another MMAE-based ADC drug
2. 2.Have regular physical exams by a doctor to check their nerves
3. 3.Have machine tests to measure how well their nerves work
4. 4.Answer survey questions about their pain, numbness, and daily activities

Conditions

Bladder Cancer; Metastatic Urothelial Carcinoma; Urothelial Carcinoma; Peripheral Neuropathy

Keywords

Peripheral Neuropathy; Sacituzumab Tirumotecan; Enfortumab Vedotin; MMAE; Disitamab Vedotin

Outcome Measures

Primary Outcomes (1)

• Peripheral Neuropathy Progression Rate (PNPR)

  The PNPR is defined as the proportion of participants who experience their first occurrence of treatment-emergent peripheral neurotoxicity of Grade 2 or higher from the time of randomization until the end of treatment. Neurotoxicity severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, a 5-point ordinal scale ranging from Grade 1 (mild; asymptomatic or mild symptoms, clinical or diagnostic observations only) to Grade 5 (death related to adverse event). Higher grades indicate worse outcomes (i.e., more severe neurotoxicity). The difference in PNPR between treatment arms will be analyzed using the Cochran-Mantel-Haenszel (CMH) test, adjusted for stratification factors specified in the protocol.

  From randomization up to the end of treatment (approximately 24 months).

Secondary Outcomes (10)

• Percent Change in NCS Parameters

  Baseline, and at protocol-specified time points (including the time of first occurrence of Grade ≥2 neurotoxicity symptoms) during the treatment period, up to approximately 24 months.

• Cumulative Neurotoxicity Burden (CNB)

  From randomization up to the end of treatment (approximately 24 months).

• Health-Related Quality of Life: EORTC QLQ-C30

  From randomization up to the end of treatment (approximately 24 months), assessed at baseline and at protocol-specified time points.

• Chemotherapy-Induced Peripheral Neuropathy Symptoms: EORTC QLQ-CIPN20

  From randomization up to the end of treatment (approximately 24 months), assessed at baseline and at protocol-specified time points.

• Objective Response Rate (ORR)

  From randomization up to the end of treatment (approximately 24 months).

Other Outcomes (1)

• Serum Neurofilament Light Chain (sNfL) Levels

  Baseline, and at protocol-specified time points during treatment (including the time of first occurrence of Grade ≥2 neurotoxicity symptoms), up to approximately 24 months.

Study Arms (3)

Experimental

EXPERIMENTAL

Patients receive sac-TMT (a Topo-I inhibitor-payload ADC) following failure of prior MMAE-based ADC therapy.

Drug: Sacituzumab Tirumotecan

Active Comparator

ACTIVE COMPARATOR

Patients receive an alternative MMAE-based ADC regimen as sequential therapy following progression on or intolerance to prior MMAE-based ADC treatment.

Drug: MMAE-based ADC

Observational

OTHER

An observational cohort for patients who discontinued prior MMAE-ADCs due to neurotoxicity.

Drug: Sacituzumab Tirumotecan (Observational Cohort)

Interventions

Sacituzumab Tirumotecan DRUG

4.0 mg/kg intravenously administered on Day 1 every 2 weeks.

Also known as: sac-TMT, SKB264, MK-2870

Experimental

MMAE-based ADC DRUG

EV (Enfortumab Vedotin): 1.25 mg/kg administered intravenously on Days 1, 8, and 15 of every 4 weeks. DV (Disitamab Vedotin): 2.0 mg/kg administered intravenously on Day 1 of every 2 weeks.

Also known as: EV, DV

Active Comparator

Sacituzumab Tirumotecan (Observational Cohort) DRUG

4.0 mg/kg intravenously administered on Day 1 every 2 weeks.

Also known as: sac-TMT, SKB264, MK-2870

Observational

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Peripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Yao Zhu

CONTACT

+86 13816751347; zhuyao@fudan.edu.cn

Shanshan Wang

CONTACT

+86 13918029242; fuscc_wangshanshan@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a Phase II study consisting of a randomized, head-to-head interventional part and a concurrent observational cohort.

Study Record Dates

• First Submitted: May 10, 2026
• First Posted: June 23, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)