Derazantinib and Atezolizumab in Patients With Urothelial Cancer
- Conditions
- Urothelial Carcinoma
- Interventions
- Registration Number
- NCT04045613
- Lead Sponsor
- Basilea Pharmaceutica
- Brief Summary
The purpose of this study was 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 comprised five open-label substudies (1-5) in patients with advanced urothelial cancer harboring FGFR GA (with the exception of substudy 2 which did not require a FGFR GA) who were treated by derazantinib monotherapy or derazantinib in combination with atezolizumab. The study enrolled patients with cisplatin-ineligible status, or patients whose disease progressed after either first-line treatment or prior treatment with FGFR inhibitors.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 95
- 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) (Note; Substudy 2 started with patients requiring an FGFR GA, but this requirement was removed from the protocol later on)
- Measurable disease, as defined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
- Adequate organ functions as indicated by Screening visit local laboratory values
- Receipt of prior cancer treatment within specific interval periods
- Concurrent evidence of any clinically significant corneal or retinal disorder
- History of clinically significant cardiac disorders
- Known CNS metastases
- Concurrent uncontrolled or active infection with human immunodeficiency virus
- Active hepatitis B or chronic hepatitis B without current antiviral therapy
- Active hepatitis C
- Active tuberculosis
- Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 3: Derazantinib 200 mg twice daily + atezolizumab 1200 mg Derazantinib 200 mg twice daily + atezolizumab 1200 mg Patients with urothelial cancer were treated with derazantinib 200 mg twice daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion Substudy 1: Derazantinib 300 mg once daily Derazantinib 300 mg once daily monotherapy Patients with urothelial cancer were treated with derazantinib 300 mg once daily Substudy 5: Derazantinib 200 mg twice daily Derazantinib 200 mg twice daily monotherapy Patients with urothelial cancer were treated with derazantinib 200 mg twice daily Substudy 4 (Cohort 4b):Derazantinib 300 mg once daily + atezolizumab 1200 mg Derazantinib 300 mg once daily + atezolizumab 1200 mg Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion Substudy 2 (Dose-Level 1): Derazantinib 200 mg once daily + atezolizumab 1200 mg Derazantinib 200 mg once daily + atezolizumab 1200 mg Patients with any solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as intravenous (IV) infusion Substudy 2 (Dose-Level 2): Derazantinib 300 mg once daily + atezolizumab 1200 mg Derazantinib 300 mg once daily+ atezolizumab 1200 mg Patients with any solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion Substudy 4 (Cohort 4a):Derazantinib 300 mg once daily Derazantinib 300 mg once daily monotherapy (QD) Patients with FGFR inhibitor resistant urothelial cancer were treated with derazantinib 300 mg once daily
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2) From first dose up to 2 years The RP2D was determined by a joint decision taken by the Independent Data Monitoring Committee (IDMC), Investigators, and the Sponsor in reviewing the aggregate of DLT and AE data, and considering efficacy data
Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) From first dose up to 2 years ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded investigator central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1
Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2 From first dose up to 2 years In Substudy 2, the primary endpoint was the number of patients with DLTs. A DLT was defined as a clinically-significant adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications. Any DLT had to be a toxicity considered at least possibly related to derazantinib or the combination of derazantinib and atezolizumab
- Secondary Outcome Measures
Name Time Method ORR Based on RECIST 1.1 (Substudy 2) From first dose up to 2 years ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded investigator central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1
Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies From first dose up to 2 years DCR was defined as the proportion of patients who achieved a confirmed clinical response (CR), partial response (PR) or stable disease (SD) by BICR using the internationally recognized criteria in accordance with RECIST Version 1.1
Number of Patients With at Least Grade 3 Adverse Events (AEs) From first dose and until 90 days following the last dose Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 )
Duration of Response (DOR) Per RECIST 1.1 From first dose up to 2 years DOR was calculated from the first date of documented tumor response (confirmed CR or PR) to the date of disease progression as assessed by BICR or death per RECIST 1.1
Progression-free Survival (PFS) by RECIST in All Substudies From first dose up to 2 years PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first
Overall Survival (OS) in All Substudies From first dose up to 2 years OS was calculated from the date of cohort assignment until death from any cause
Related Research Topics
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Trial Locations
- Locations (66)
CTCA Clinical Research Inc., Atlanta
🇺🇸Newnan, Georgia, United States
Englander Institute Weill Cornell Medicine
🇺🇸New York, New York, United States
New York Cancer and Blood Specialists
🇺🇸Port Jefferson Station, New York, United States
University of Texas Southwestern Medical Center (UTSWMC)
🇺🇸Dallas, Texas, United States
MD Anderson
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Medical Oncology Associates PS (dba Summit Cancer Centers)
🇺🇸Spokane, Washington, United States
Coastal Cancer Care
🇦🇺Birtinya, Australia
Canberra Hospital and Health Services
🇦🇺Canberra, Australia
John Flynn Private Hospital
🇦🇺Tugun, Australia
Scroll for more (56 remaining)CTCA Clinical Research Inc., Atlanta🇺🇸Newnan, Georgia, United States