Enfortumab vedotin and pembrolizumab vs. chemotherapy alone in untreated locally advanced or metastatic urothelial cancer
- Conditions
- rothelial Cancer
- Registration Number
- JPRN-jRCT2031200284
- Lead Sponsor
- Gorla Seema
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 990
Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
- Measurable disease by investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
o Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
- Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
o Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
o Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
- Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment
- Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
- Adequate hematologic and organ function
- Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
- Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
- Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
- Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
- Uncontrolled diabetes
- Estimated life expectancy of less than 12 weeks
- Active central nervous system (CNS) metastases
- Ongoing clinically significant toxicity associated with prior treatment that has not resolved to =< Grade 1 or returned to baseline
- Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
- Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
- History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
- Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
- Receipt of radiotherapy within 2 weeks prior to randomization
- Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
- Known severe (>= Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
- Active keratitis or corneal ulcerations
- History of autoimmune disease that has required systemic treatment in the past 2 years
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Prior allogeneic stem cell or solid organ transplant
- Received a live attenuated vaccine within 30 days prior to randomization
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Japan-specific safety run-in<br>-Type, incidence, relatedness, severity and seriousness of adverse events (AEs) including dose limiting toxicities (DLTs)<br>-Type, incidence and severity of laboratory abnormalities<br>-Treatment discontinuation rate due to AEs<br>For global study:<br>-Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR) <br>-Duration of Overall survival (OS)
- Secondary Outcome Measures
Name Time Method For global study:<br>-PFS per RECIST v1.1 by investigator assessment<br>-Objective response rate (ORR) per RECIST v1.1 by BICR<br>-ORR per RECIST v1.1 by investigator assessment <br>-Duration of response (DOR) per RECIST v1.1 by BICR<br>-DOR per RECIST v1.1 by investigator assessment <br>-Disease control rate (DCR) per RECIST v1.1 by BICR<br>-DCR per RECIST v1.1 by investigator assessment<br>- Time to pain progression (TTPP)<br>- Mean change from baseline in worst pain at Week 26<br>-Mean scores and change from baseline of the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L)<br>-Mean scores and change from baseline of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30)<br>-Incidence of adverse events (AEs)<br>-Incidence of laboratory abnormalities<br>-Treatment discontinuation rate due to AEs