Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Neoplasm Metastasis
Conditions
Keywords
FGFR3, Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
Brief summary
The purpose of this study is to test a new medicine, vepugratinib, in comparison with placebo, to see if it is safe and can help people with a bladder cancer that is advanced or has spread. Vepugratinib or placebo will be administered in combination with enfortumab vedotin and pembrolizumab. Study participation could last up to approximately 6 years.
Interventions
DRUGVepugratinib
Administered orally
OTHERPlacebo
Administered orally
DRUGEV
Administered by IV infusion
DRUGPembrolizumab
Administered by IV infusion
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
There will be an open-label safety lead in.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically confirmed, unresectable locally advanced or metastatic urothelial cancer (mUC). Individuals with mixed histology other than small cell or neuroendocrine carcinoma are eligible if a urothelial component is present. * Have a qualifying fibroblast growth factor receptor 3 (FGFR3) genetic alteration determined via molecular testing from a tumor or blood sample obtained at or any time after diagnosis of advanced or metastatic urothelial cancer. * Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Have adequate laboratory parameters
Exclusion criteria
* Have received prior systemic therapy for locally advanced or metastatic urothelial cancer (mUC). * Have any unresolved toxicities greater than Grade 1 Common Terminology Criteria for Adverse Events (\[CTCAE\] version 5.0) from prior neoadjuvant or adjuvant systemic therapy. * Have ongoing sensory or motor neuropathy of Grade 2 or higher * Have untreated or uncontrolled central nervous system (CNS) involvement or any history of leptomeningeal disease. * Current evidence corneal keratopathy or retinal disorder confirmed by ocular examination at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab | From baseline up to 90 months | — |
| Safety Lead-in: Overall Response Rate (ORR) | From baseline up to 90 months | ORR by Investigator Assessment. |
| Progression-free Survival (PFS) | Baseline to Study Completion (estimated as 6 years) | PFS by blinded independent committee review (BICR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Lead-in: Disease Control Rate (DCR) | From baseline up to the end of Cycle 2 (each Cycle is 21 days) | DCR by investigator assessment. |
| Safety Lead-in: Time to Response (TTR) | From baseline up to 90 months | TTR by investigator assessment. |
| Overall Survival (OS) | Baseline to Study Completion (estimated as 6 years) | — |
| Objective Response Rate (ORR) by BICR | Baseline to Study Completion (estimated as 6 years) | — |
| Duration of Response (DoR) | Baseline to Study Completion (estimated as 6 years) | DOR by BICR. |
| Progression-free Survival (PFS) | Baseline to Study Completion (estimated as 6 years) | PFS by investigator assessment. |
| Objective Response Rate (ORR) | Baseline to Study Completion (estimated as 6 years) | Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)ORR by investigator assessment |
| Duration of Response (DOR) | Baseline to Study Completion (estimated as 6 years) | DOR by investigator assessment. |
| Progression-free Survival 2 (PFS2) | Baseline to Study Completion (estimated as 6 years) | PFS2 by investigator assessment. |
| Plasma Concentrations of Vepugratinib | Cycle 1 Day 1 to Study completion (estimated as 90 months) | PK samples are to be drawn every odd cycle while participant on study. |
| Change from Baseline in Global Health Status/Quality of Life (QOL) and Physical Function Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline to Study Completion (estimated as 6 years) | The EORTC QLQ-C30 is a validated self-reported general cancer questionnaire consisting of 30 items with a recall of the past 7 days. Response options range from 1) "very poor" to 7) "excellent." Higher scores represent better overall HRQoL. |
Countries
Australia, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed