Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 3
Seagen, a wholly owned subsidiary of Pfizer (Voir sur ClinicalTrials)
septembre 2023
avril 2029
08 août 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Europeen Georges Pompidou | Contact (sur clinicalTrials) | ||||
| CLCC INSTITUT GUSTAVE ROUSSY | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre de Lutte contre le Cancer - François Baclesse - 14076 - Caen Cedex 5 - France | Contact (sur clinicalTrials) | ||||
| Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne - 06189 - Nice Cedex 2 - France | Contact (sur clinicalTrials) | ||||
| Hospices Civils de Lyon - 69310 - Pierre Benite - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonié Centre de Lutte Contre le Cancer (CLCC) - 33076 - Bordeaux Cedex - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancerologie Strasbourg Europe - 67200 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli Calmettes - 13009 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Institut régional du Cancer de Montpellier - ICM Val d'Aurelle - 34298 - MONTPELLIER Cedex 5 - France | Contact (sur clinicalTrials) | ||||
| Pharmacy ICM Val d'Aurelle - Bat A - Rez-de-Jardin - 34298 - MONTPELLIER Cedex 5 - France | Contact (sur clinicalTrials) | ||||
| Unite de Coordination de la Biologie des Essais Cliniques - 67091 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| University Hospital of Besancon - 25000 - Besancon - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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.
- 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.
- 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