Description:
The purpose of this study is to evaluate efficacy of derazantinib monotherapy or
derazantinib-atezolizumab in combination in patients with advanced urothelial cancer
harboring fibroblast growth factor receptor (FGFR) genetic aberrations (GA) of various
clinical stages of disease progression and prior treatments.
Title
- Brief Title: Derazantinib and Atezolizumab in Patients With Urothelial Cancer
- Official Title: An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations
Clinical Trial IDs
- ORG STUDY ID:
DZB-CS-201
- SECONDARY ID:
2019-000359-15
- NCT ID:
NCT04045613
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Derazantinib dose level 1 (300mg once daily) monotherapy | | Derazantinib +/- atezolizumab: Second line [Substudy 4] |
| Derazantinib various dose levels in combination with atezolizumab | | Derazantinib + atezolizumab: Dose finding [Substudy 2] |
| Derazantinib dose level 2 (200 mg twice daily) monotherapy | | Derazantinib monotherapy [Substudy 5] |
| Derazantinib dose level 1 in combination with atezolizumab | | Derazantinib +/- atezolizumab: Second line [Substudy 4] |
| Derazantinib dose level 2 in combination with atezolizumab | | Derazantinib + atezolizumab: First line [Substudy 3] |
Purpose
The purpose of this study is to evaluate efficacy of derazantinib monotherapy or
derazantinib-atezolizumab in combination in patients with advanced urothelial cancer
harboring fibroblast growth factor receptor (FGFR) genetic aberrations (GA) of various
clinical stages of disease progression and prior treatments.
Detailed Description
The study comprises five open-label substudies in patients with advanced urothelial cancer
harboring FGFR GA who will be treated by derazantinib monotherapy or derazantinib in
combination with atezolizumab. The study enrolls patients with cisplatin-ineligible status,
or patients whose disease progressed after either first-line treatment or prior treatment
with FGFR inhibitors.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Derazantinib monotherapy [Substudy 1] | Experimental | Patients with urothelial cancer who have progressed on at least one line of standard treatment will be treated with derazantinib dose level 1. | - Derazantinib dose level 1 (300mg once daily) monotherapy
|
| Derazantinib + atezolizumab: Dose finding [Substudy 2] | Experimental | Dose finding and dose expansion in patients with solid tumor. | - Derazantinib various dose levels in combination with atezolizumab
|
| Derazantinib + atezolizumab: First line [Substudy 3] | Experimental | Patients with urothelial cancer will be treated with a combination of derazantinib and atezolizumab. | - Derazantinib dose level 2 in combination with atezolizumab
|
| Derazantinib +/- atezolizumab: Second line [Substudy 4] | Experimental | Patients with urothelial cancer progressing after prior FGFR inhibitor treatment will be randomized to receive either derazantinib alone or a combination of derazantinib and atezolizumab. | - Derazantinib dose level 1 (300mg once daily) monotherapy
- Derazantinib dose level 1 in combination with atezolizumab
|
| Derazantinib monotherapy [Substudy 5] | Experimental | Patients with urothelial cancer who have progressed on at least one line of standard treatment will be treated with derazantinib dose level 2. | - Derazantinib dose level 2 (200 mg twice daily) monotherapy
|
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or
lower urinary tract
- Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or
progressing disease
- Documented central FGFR genetic aberration (FGFR1, FGFR2, or FGFR3 mutations / short
variants and rearrangements / fusions)
- Measurable disease per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
- Adequate bone marrow, liver and renal function
Exclusion Criteria:
- Receipt of chemotherapy, targeted therapies, immunotherapy, or treatment with an
investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug
whichever is longer before the first dose of study drug.
- Concurrent evidence of any clinically significant corneal or retinal disorder
- Phosphatemia greater than institutional upper limit of normal (ULN) at screening
- Uncontrolled tumor-related hypercalcemia
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Response Rate (ORR) based on RECIST 1.1 |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Disease control rate per RECIST 1.1 |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response per RECIST 1.1 |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Median progression-free survival (PFS) and PFS at 6 months |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Median overall survival (OS) and OS at 6 months |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Safety and tolerability of study treatment based on incidence of treatment-emergent adverse events |
| Time Frame: | Approximately up to 2 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Basilea Pharmaceutica |
Trial Keywords
- metastatic urothelial cancer
- bladder cancer
- Fibroblast Growth Factor Receptor
- FGFR genetic aberration
- targeted therapy
- derazantinib
- checkpoint inhibitor
- immune checkpoint blockade
- atezolizumab
- Tecentriq
- solid tumor
Last Updated
July 21, 2021
