Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2
Phase 3 – large-scale trial before approval
Conditions:
Urothelial Carcinoma
Sponsor: Seagen, a wholly owned subsidiary of Pfizer
trial.available_in:
БГ
Overview
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.
Who can participate
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
Interventions
disitamab vedotin
DRUG
pembrolizumab
DRUG
gemcitabine
DRUG
cisplatin
DRUG
carboplatin
DRUG
Locations
279
Argentina (16)
Centro de Oncologia e Investigacion de Buenos Aires (COIBA)
Berazategui
Centro Medico Austral
Buenos Aire
Centro de Investigaciones Medicas y Desarrollo LC
Buenos Aires , Buenos Aires F.D.
Instituto Médico Especializado Alexander Fleming
Buenos Aires
Centro Oncologico Korben
Buenos Aires
Investigaciones Clinicas Moleculares (ICM)
CABA
Labmedicina
CABA
CEMAIC - Centro Medico Privado
Córdoba
Centro de Investigacion Pergamino SA
Pergamino , Buenos Aires
Sanatorio Parque
Rosario , Santa Fe Province
Comité Provincial de Bioética-Rosario
Rosario
Grupo de Investigación en Oncología Clínica del Santario Parque
Rosario
Consultorio Dr. Miguel Angel Escudero
Salta
Oncologia Salta
Salta
Fundación Dr. Ruben Kowalyszyn
Viedma , Río Negro Province
Clinica Viedma
Viedma , Río Negro Province
Australia (17)
Mater Misericordiae - Mater Hospital Brisbane
Brisbane , Queensland
South Eastern Sydney Local Health District
Caringbah
ICON Cancer Centre Chermside
Chermside , Queensland
Concord Cancer Centre Concord Repatriation General Hospital
Concord , New South Wales
Saint Vincents Hospital Sydney - Human Research Ethics Committee
Darlinghurst , New South Wales
St Vincent's Clinic
Darlinghurst , New South Wales
Lyell McEwin Hospital
Elizabeth Vale
Peninsula & South Eastern Hematology and Oncology Group (PASO)
Frankston , Victoria
Peninsula And South East Oncology
Frankston
Icon Cancer Centre Chermside
Herston , Queensland
Macquarie University Hospital
Macquarie University , New South Wales
Cabrini Hospital
Malvern , Victoria
Macquarie University
North Ryde , New South Wales
Mid North Coast Local Health District
NSW
Port Macquarie Base Hospital
Port Macquarie
Prince of Wales Hospital
Randwick , New South Wales
Mater Research
South Bribane , Queensland
Belgium (3)
Algemeen Ziekenhuis Maria Middelares
Ghent
AZ St. Lucas
Ghent
University Hospital Ghent
Ghent
Brazil (14)
Hospital de Cancer de Barretos - Fundacao Pio XII
Barretos
Associacao Mario Penna - Hospital Luxemburgo - NEPI Nucleo de Ensino Pesquisa e Inovacao
Belo Horizonte , Minas Gerais
Erasto Gaertner Hospital
CuriBba
Suporte Nutricional e Quimioterapia - PRONUTRIR
Fortaleza , Ceará
Fundacao Doutor Amaral Carvalho
Jaú , São Paulo
Hospital Sao Vicente de Paulo
Passo Fundo , Rio Grande do Sul
Hospital Sao Vicente de Paulo
Passo Fundo , Rio Grande do Sul
Hospital Mae de Deus
Porto Alegre , Rio Grande do Sul
Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)
Porto Alegre , Rio Grande do Sul
Hospital Nossa Senhora da Conceicao / Grupo Hospitalar Conceicao
Porto Alegre , Rio Grande do Sul
Instituto Nacional De Cancer - INCA
Rio de Janeiro
Instituto Nacional De Cancer - INCA
Rio de Janeiro
Centro de Oncologia da Bahia
Salvador
Hospital Alemao Oswaldo Cruz
São Paulo
Canada (5)
Arthur J.E. Child Comprehensive Cancer Centre
Calgary , Alberta
University of Alberta / Cross Cancer Institute
Edmonton , Alberta
Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)
Oshawa , Ontario
University Health Network
Toronto , Ontario
Princess Margaret Cancer Centre - University Health Network
БГ