Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2
- Conditions
- Interventions
- Registration Number
- NCT05911295
- Lead Sponsor
- Seagen Inc.
- Brief Summary
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...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 700
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care arm gemcitabine gemcitabine + cisplatin OR carboplatin Disitamab vedotin arm disitamab vedotin disitamab vedotin + pembrolizumab Disitamab vedotin arm pembrolizumab disitamab vedotin + pembrolizumab Standard of care arm carboplatin gemcitabine + cisplatin OR carboplatin Standard of care arm cisplatin gemcitabine + cisplatin OR carboplatin
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR) 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.
Overall survival (OS) Approximately 5 years The time from date of randomization to date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Number of electrocardiogram (ECG) abnormalities Through 30 days after the last study treatment; approximately 2 years Duration of Response (DOR) per RECIST v1.1 by BICR 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.
Control Rate (DCR) per RECIST v1.1 by BICR Approximately 3 years The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.
Number of participants with adverse events (AEs) 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.
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 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.
Objective response rate (ORR) per RECIST v1.1 by BICR Approximately 3 years The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.
ORR per RECIST v1.1 by investigator assessment Approximately 3 years The proportion of participants with confirmed CR or PR according to RECIST v1.1.
DOR per RECIST v1.1 by investigator assessment 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.
DCR per RECIST v1.1 by investigator assessment Approximately 3 years The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.
PFS per RECIST v1.1 by investigator assessment Approximately 3 years The time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause.
Change from baseline of left ventricular ejection fraction (LVEF) Through 2 years after last study treatment; approximately 4 years Time to pain progression 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,
...Number of participants with laboratory abnormalities Through 30 days after the last study treatment; approximately 2 years Treatment discontinuation rate due to AEs Approximately 2 years Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score 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 r...
Trial Locations
- Locations (116)
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Hospital de Cancer de Barretos - Fundacao Pio XII
🇧🇷Barretos, Other, Brazil
Centro de Oncologia da Bahia
🇧🇷Salvador, Other, Brazil
Arthur J.E. Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Alaska Oncology and Hematology
🇺🇸Anchorage, Alaska, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
The Oncology Institute of Hope & Innovation - California
🇺🇸Cerritos, California, United States
Los Angeles Cancer Network / Compassionate Care Research Group
🇺🇸Fountain Valley, California, United States
University of California Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Pacific Cancer Care
🇺🇸Monterey, California, United States
Kaiser Permanente Southern California
🇺🇸Riverside, California, United States
University of California, San Francisco | HDFCCC - Hematopoietic Malignancies
🇺🇸San Francisco, California, United States
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
PIH Health Hospital Whittier
🇺🇸Whittier, California, United States
Decatur Memorial Hospital - Illinois
🇺🇸Decatur, Illinois, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
Siouxland Regional Cancer Center dba June E. Nylen Cancer Center
🇺🇸Sioux City, Iowa, United States
Greater Baltimore Medical Center (GBMC) - Sandra & Malcolm Berman Cancer Institute
🇺🇸Baltimore, Maryland, United States
University of Minnesota
🇺🇸Burnsville, Minnesota, United States
HealthPartners Institute
🇺🇸Saint Louis Park, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Cancer Partners of Nebraska
🇺🇸Lincoln, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
OptumCare Cancer Center
🇺🇸Las Vegas, Nevada, United States
North Shore Center for Advanced Medicine Monter Cancer Center / North Shore University Hospital
🇺🇸Lake Success, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
ECU Health Medical Center
🇺🇸Greenville, North Carolina, United States
MidLantic Urology
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
West Cancer Center & Research Institute
🇺🇸Germantown, Tennessee, United States
Thompson Cancer Survival Center
🇺🇸Knoxville, Tennessee, United States
University of Tennessee
🇺🇸Knoxville, Tennessee, United States
US Oncology Central Regulatory
🇺🇸The Woodlands, Texas, United States
Providence Regional Medical Center Everett
🇺🇸Everett, Washington, United States
Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin (Milwaukee)
🇺🇸Milwaukee, Wisconsin, United States
Centro Oncologico Korben
🇦🇷Buenos Aires, Other, Argentina
Centro Medico Austral
🇦🇷Buenos Aire, Other, Argentina
Investigaciones Clinicas Moleculares (ICM)
🇦🇷Caba, Other, Argentina
CEMAIC - Centro Medico Privado
🇦🇷Cordoba, Other, Argentina
Sanatorio Parque
🇦🇷Rosario, Other, Argentina
Oncologia Salta
🇦🇷Salta, Other, Argentina
Clinica Viedma
🇦🇷Viedma, Other, Argentina
Fundacion Cenit
🇦🇷Caba, Argentina
Macquarie University Hospital
🇦🇺Brisbane, Other, Australia
Icon Cancer Care Chermside
🇦🇺Chermside, Other, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, Other, Australia
Peninsula and South East Oncology
🇦🇺Frankston, Other, Australia
Port Macquarie Base Hospital
🇦🇺Port Macquarie, Other, Australia
Mater Cancer Care Centre
🇦🇺South Brisbane, Other, Australia
Royal North Shore Hospital
🇦🇺St Leonards, Other, Australia
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, Other, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, Other, Brazil
University of Alberta / Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)
🇨🇦Oshawa, Ontario, Canada
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Other, Canada
Centro De Investigaciones Clinicas Vina Del Mar
🇨🇱Vina del mar, Other, Chile
University Hospital of Besancon
🇫🇷Besancon cedex, Other, France
Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie
🇫🇷Bordeaux, Other, France
Institut Paoli Calmettes
🇫🇷Marseille, Other, France
Institut Regional du Cancer de Montpellier
🇫🇷Montpellier, Other, France
Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, Other, France
Hospices Civils de Lyon
🇫🇷Pierre Benite, Other, France
Institut de cancerologie Strasbourg Europe
🇫🇷Strasbourg, Other, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, Other, France
HaEmek Medical Center
🇮🇱Afula, Other, Israel
Soroka Medical Center, Dept. of Oncology
🇮🇱Hadarom, Other, Israel
Rambam Health Corp.
🇮🇱Haifa, Other, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Other, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Other, Israel
Meir Medical Center
🇮🇱Kfar Saba, Other, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Other, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Other, Israel
Kaplan Medical Center
🇮🇱Rehovot, Other, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Other, Israel
Azienda Ospedaliera Istituti Ospedalieri di Cremona
🇮🇹Cremona, Other, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Other, Italy
Azienda Ospedaliera S. Maria di Terni
🇮🇹Terni, Other, Italy
Azienda Ospedaliera Universitaria Integrata di Verona
🇮🇹Verona, Other, Italy
Inje University Haeundae Paik Hospital
🇰🇷Busan, Other, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Other, Korea, Republic of
Wonkwang University Hospital
🇰🇷Iksan, Other, Korea, Republic of
National Cancer Center
🇰🇷Ilsandong-gu, Other, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Other, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju-si, Other, Korea, Republic of
CHA Bundang Medical Center
🇰🇷Seongnam-si, Other, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Other, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Other, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Other, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Other, Korea, Republic of
Asan Medical Center - Oncology
🇰🇷Seoul, Other, Korea, Republic of
St. Vincent's Hospital, The Catholic University of Korea
🇰🇷Suwon-si, Other, Korea, Republic of
Hospital Militar Central
🇵🇪Lima, Other, Peru
Hospital Maria Auxiliadora
🇵🇪Lima, Peru
National University Hospital
🇸🇬Singapore, Other, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Other, Singapore
Raffles Hospital
🇸🇬Singapore, Other, Singapore
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Other, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Other, Spain
MD Anderson Cancer Center - Madrid
🇪🇸Madrid, Other, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Other, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Other, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Other, Spain
HM Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Other, Spain
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Other, Spain
Complejo Hospitalario Universitario de Ourense (CHOU)
🇪🇸Ourense, Other, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Other, Spain
Valencian Institute of Oncology Foundation
🇪🇸Valencia, Spain
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Other, Taiwan
China Medical University Hospital
🇨🇳Taichung, Other, Taiwan
Chi Mei Hospital Liouying
🇨🇳Tainan, Other, Taiwan
National Cheng-Kung University Hospital
🇨🇳Tainin, Other, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Other, Taiwan
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