Clinical trial NCT04045613: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Urothelial Carcinoma
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
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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) (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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)
timeFrame: From first dose up to 2 years
measure: Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)
timeFrame: From first dose up to 2 years
measure: Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2
timeFrame: From first dose up to 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies
timeFrame: From first dose up to 2 years
measure: Duration of Response (DOR) Per RECIST 1.1
timeFrame: From first dose up to 2 years
measure: ORR Based on RECIST 1.1 (Substudy 2)
timeFrame: From first dose up to 2 years
measure: Progression-free Survival (PFS) by RECIST in All Substudies
timeFrame: From first dose up to 2 years
measure: Overall Survival (OS) in All Substudies
timeFrame: From first dose up to 2 years
measure: Number of Patients With at Least Grade 3 Adverse Events (AEs)
timeFrame: From first dose and until 90 days following the last dose
Other outcomes:
Locations:
city: Newnan
country: United States
facility: CTCA Clinical Research Inc., Atlanta
state: Georgia
city: New York
country: United States
facility: Englander Institute Weill Cornell Medicine
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center (UTSWMC)
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates PS (dba Summit Cancer Centers)
state: Washington
city: Birtinya
country: Australia
facility: Coastal Cancer Care
city: Canberra
country: Australia
facility: Canberra Hospital and Health Services
city: Tugun
country: Australia
facility: John Flynn Private Hospital
city: Wendouree
country: Australia
facility: Ballarat Oncology & Haematology Services
city: Westmead
country: Australia
facility: Westmead Hospital
city: Vienna
country: Austria
facility: Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH) - Universitaetsklinik fuer Urologie
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre François Baclesse
city: Marseille
country: France
facility: CHU Timone / CEPCM
city: Paris
country: France
facility: Medical Oncology - Pitié-Salpêtrière Hopital
city: Toulouse
country: France
facility: IUCT-Oncopole de Toulouse
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Campus Charite Mitte
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Erlangen
country: Germany
facility: University Clinic Erlangen
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg A.oe.R
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Kecskemét
country: Hungary
facility: Bacs- Kiskun Megyei Korhaz
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IRCCS - Istituto Europeo di Oncologia IEO
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Sondrio
country: Italy
facility: ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Marys Hospital Catholic University of Korea
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o. o.
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., 04-073, Warszawa, Poland
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny
city: Barcelona
country: Spain
facility: Vall d Hebron Hospital
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: IOB - Hospital Quiron Salud
city: Barcelona
country: Spain
facility: ICO Hospitalet
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro CIOCC
city: Santander
country: Spain
facility: Marques de Valdecilla University Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Lausanne
country: Switzerland
facility: Lausanne University Hospital
city: Zürich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: London
country: United Kingdom
facility: Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)
city: London
country: United Kingdom
facility: The Sarah Cannon Research Institute
city: London
country: United Kingdom
facility: University College London Hospitals
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Basilea Pharmaceutica International Ltd, Allschwil
name: Manuel Häckl, MD
role: STUDY_DIRECTOR
References: