Urothelial Carcinoma
Conditions
Interventions
Experimental Arm
- Disitamab vedotin 1.5 mg/kg administered intravenously (IV) every 2 weeks + pembrolizumab 400 mg IV every 6 weeks
Control arm
- Gemcitabine (1000 mg/m2) IV on Days 1 and 8 of every
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
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 Response Evaluation Criteria in Solid Tumors (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
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 programmed cell death protein 1 and programmed death-ligand 1 (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 a monomethyl auristatin E (MMAE) agent or anti-HER2 therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) - Overall survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Objective response rate (ORR) per RECIST v1.1 by BICR - ORR per RECIST v1.1 by investigator assessment - Duration of Response (DOR) per RECIST v1.1 by BICR - DOR per RECIST v1.1 by investigator assessment - Disease control rate (DCR) per RECIST v1.1 by BICR - DCR per RECIST v1.1 by investigator assessment - PFS per RECIST v1.1 by investigator assessment - Number of participants with adverse events (AEs) - Number of participants with laboratory abnormalities - Treatment discontinuation rate due to AEs - Number of electrocardiogram abnormalities - Change from baseline of left ventricular ejection fraction - 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 to Deterioration in EORTC QLQ-C30 GHS/QoL Score - Time to pain progression | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Netherlands, Peru, Portugal, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed