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New treatment for advanced urothelial cancer using disitamab vedotin and pembrolizumab

An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination With Pembrolizumab Versus Chemotherapy in Subjects With Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma That Expresses HER2 (IHC 1+ and Greater)

Phase 3 Interventional Seagen Inc. · NCT05911295

This study is testing a new combination of disitamab vedotin and pembrolizumab to see if it works better than standard chemotherapy for people with advanced urothelial cancer who haven't been treated before.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorSeagen Inc. Industry-sponsored
Drugs / interventionsdisitamab, pembrolizumab, CAR-T, chemotherapy, prednisone
Locations317 sites (Gilbert, Arizona and 316 other locations)
Trial IDNCT05911295 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of disitamab vedotin combined with pembrolizumab compared to standard platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Participants will be randomly assigned to receive either the experimental drug combination or standard chemotherapy. The study will also assess the safety and side effects associated with the new treatment regimen. Eligible patients must have measurable disease and HER2 expression of 1+ or greater.

Who should consider this trial

Good fit: Ideal candidates are individuals with locally advanced or metastatic urothelial carcinoma who have not received prior systemic therapy and have HER2 expression of 1+ or greater.

Not a fit: Patients with urothelial carcinoma who have already undergone systemic therapy or do not express HER2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced urothelial cancer, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in urothelial carcinoma, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
* Measurable disease by investigator assessment per RECIST v1.1.
* Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
* Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
* Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
* HER2 expression of 1+ or greater on immunohistochemistry (IHC).
* Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization.

Exclusion Criteria:

* Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
* History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.
* Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.

  * CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
  * Participant is on a stable dose of ≤ 10 mg/day of prednisone or equivalent for at least 2 weeks.
* History of or active autoimmune disease that has required systemic treatment in the past 2 years.
* Prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists).
* Prior solid organ or bone marrow transplantation.
* Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
* Estimated life expectancy \<12 week
* Prior treatment with an MMAE agent or anti-HER2 therapy

Where this trial is running

Gilbert, Arizona and 316 other locations

+267 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Urothelial CarcinomaUrothelial CancerLA/mUCBladder CancerHER2 OverexpressionHER2 AmplificationHER2Seattle Genetics
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.