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NCT Number: NCT05911295

Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2

This study will enroll participants with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry pee 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 patients 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 that has spread through the body (metastatic) or spread near where it started (locally advanced).

In this study, there are 2 different groups. Participants will be assigned to a group randomly. Participants in the disitamab vedotin arm will get the study drug disitamab vedotin once every two weeks and pembrolizumab once every 6 weeks. Participants in the standard of care arm will get gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Urothelial Carcinoma Carcinoma Carcinoma, Transitional Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Investigacion Pergamino SA, Pergamino, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Disitamab Vedotin

Drug

Given into the vein (IV; intravenous) every 2 weeks

Other names: RC48, RC48-ADC

Pembrolizumab

Drug

400mg given by IV every 6 weeks

Other names: KEYTRUDA®

Gemcitabine

Drug

1000 mg/m^2 given by IV on days 1 and 8 of every 3-week cycle

Other names: Gemzar

Cisplatin

Drug

70 mg^2 given by IV on day 1 of every 3-week cycle

carboplatin

Drug

Area under the plasma concentration-time curve (AUC) 4.5 or 5 given by IV on day 1 of every 3-week cycle

Primary outcomes

  1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)

    Time frame: Approximately 3 years

    The time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause.

  2. Overall survival (OS)

    Time frame: Approximately 5 years

    The time from date of randomization to date of death due to any cause.

Secondary outcomes

  1. Objective response rate (ORR) per RECIST v1.1 by BICR

    Time frame: Approximately 3 years

    The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.

  2. ORR per RECIST v1.1 by investigator assessment

    Time frame: Approximately 3 years

    The proportion of participants with confirmed CR or PR according to RECIST v1.1.

  3. Duration of Response (DOR) per RECIST v1.1 by BICR

    Time frame: Approximately 3 years

    The time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause.

  4. DOR per RECIST v1.1 by investigator assessment

    Time frame: Approximately 3 years

    The time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause.

  5. Control Rate (DCR) per RECIST v1.1 by BICR

    Time frame: Approximately 3 years

    The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.

  6. DCR per RECIST v1.1 by investigator assessment

    Time frame: Approximately 3 years

    The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.

  7. PFS per RECIST v1.1 by investigator assessment

    Time frame: Approximately 3 years

    The time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause.

  8. Number of participants with adverse events (AEs)

    Time frame: Through 30 days after the last study treatment; approximately 2 years

    Any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  9. Number of participants with laboratory abnormalities

    Time frame: Through 30 days after the last study treatment; approximately 2 years

  10. Treatment discontinuation rate due to AEs

    Time frame: Approximately 2 years

  11. Number of electrocardiogram (ECG) abnormalities

    Time frame: Through 30 days after the last study treatment; approximately 2 years

  12. Change from baseline of left ventricular ejection fraction (LVEF)

    Time frame: Through 2 years after last study treatment; approximately 4 years

  13. Change from baseline to Week 16 in European Organization for Research and Treatment of Cancer core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QoL Score

    Time frame: Approximately 2 years

    The EORTC QLQ-C30 is used to evaluate health-related quality of life, functioning, disease symptoms, and treatment-related side effects. Scores range from 0-100. For GHS/QoL and functional scales, higher scores represent higher QoL or functioning. For symptom scales, higher scores represent more symptoms/worse status.

  14. Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score

    Time frame: Approximately 2 years

    The time from the date of randomization to the date of first deterioration (change from baseline ≥10) in GHS/QoL score with no subsequent recovery. The EORTC QLQ-C30 is used to evaluate health-related quality of life, functioning, disease symptoms, and treatment-related side effects. Scores range from 0-100. For GHS/QoL and functional scales, higher scores represent higher QoL or functioning. For symptom scales, higher scores represent more symptoms/worse status.

  15. Time to pain progression

    Time frame: Approximately 2 years

    The time from the date of randomization to whichever of the following occurs earlier:

    • an increase in Numeric Rating Scale (NRS) for pain intensity of 2 points or more from baseline at 2 consecutive visits,
    • an increase in number of opioid or analgesic use from baseline,
    • or initiation of opioid or analgesic use. NRS for pain intensity asks participants to best describe their pain at its worst in the last 24 hours from 0 to 10. On the NRS, 0 means no pain and 10 means pain as bad as you can imagine.

Sponsors and collaborators

Lead sponsor

Seagen, a wholly owned subsidiary of Pfizer

Industry

Collaborators

  • Merck Sharp & Dohme LLC
  • RemeGen Co., Ltd.

Registry information

Official study 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)

Important dates

Study start
2023
Primary completion
2027
Study completion
2029
First posted
Jun 22, 2023
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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