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No longer recruiting (closed or complete)Last updated: 8 April 2026

KEYNOTE-D74: This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat people with urothelial carcinomaAn 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)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Urinary System Cancers Genitourinary

Age

People18+

Trial acronym

KEYNOTE-D74

Clinical summary

Summary

This study will enroll people with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry urine through the body (ureter, urethra).

This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat people with UC.

This study will also test what side effects happen when participants take these drugs together. A side effect is anything a drug does to the body besides treating the disease.

Participants in this study will have cancer thas has spread through the body (metastatic) or spread near where it started (locally advanced). Their UC must be expressing HER2, with 1+ or greater on immunochemistry (IHC)

In this study, there are two different groups. Participants will be assigned to a group randomly (by chance).

  • Participants in the disitamab vedotin arm will receive the study drug disitamab vedotin once every two weeks and pembrolizumab immunotherapy once every 6 weeks.
  • Participants in the standard of care arm will receive chemotherapy that includes gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks. 

Conditions

This trial is treating people with locally advanced or metastatic Urothelial Carcinoma that is previously untreated and expresses HER2

Eligibility

Inclusion

  • 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

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body, but it is not possible to perform surgery to remove it (unresectable).

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT05911295 *
  • 2022-501105-12-00 *
  • SGNDV-001; SGNDV-001_KN-D74

Trial sponsor

Seagen Inc.

Scientific Title

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)

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