Derazantinib and Atezolizumab in Patients With Urothelial Cancer

Urothelial Carcinoma Clinical Trial

— FIDES-02  

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 Details — Status: Completed

Administrative data

• NCT number: NCT04045613
• Other study ID #: DZB-CS-201
• Secondary ID: 2019-000359-15
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2, 2019
• Est. completion date: October 4, 2022

Study information

• Verified date: September 2023
• Source: Basilea Pharmaceutica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: October 4, 2022
• Est. primary completion date: October 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Derazantinib 300 mg once daily monotherapy
Derazantinib was administered orally at a dose of 300 mg once daily
• Derazantinib 200 mg once daily + atezolizumab 1200 mg
Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks
• Derazantinib 300 mg once daily+ atezolizumab 1200 mg
Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks
• Derazantinib 200 mg twice daily + atezolizumab 1200 mg
Derazantinib was administered orally at a dose of 200 mg twice daily in combination with atezolizumab 1200 mg every 3 weeks
• Derazantinib 300 mg once daily monotherapy (QD)
Derazantinib was administered orally at a dose of 300 mg once daily
• Derazantinib 300 mg once daily + atezolizumab 1200 mg
Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks
• Derazantinib 200 mg twice daily monotherapy
Derazantinib was administered orally at a dose of 200 mg twice daily

Locations

Country	Name	City	State
Australia	Coastal Cancer Care	Birtinya
Australia	Canberra Hospital and Health Services	Canberra
Australia	John Flynn Private Hospital	Tugun
Australia	Ballarat Oncology & Haematology Services	Wendouree
Australia	Westmead Hospital	Westmead
Austria	Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH) - Universitaetsklinik fuer Urologie	Vienna
Canada	Juravinski Cancer Center	Hamilton
Canada	Princess Margaret Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni Nemocnice Olomouc	Olomouc
France	Institut Bergonie	Bordeaux
France	Centre François Baclesse	Caen
France	CHU Timone / CEPCM	Marseille
France	Medical Oncology - Pitié-Salpêtrière Hopital	Paris
France	IUCT-Oncopole de Toulouse	Toulouse
France	Institut Gustave Roussy	Villejuif
Germany	Campus Charite Mitte	Berlin
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	University Clinic Erlangen	Erlangen
Germany	Universitaetsklinikum Magdeburg A.oe.R	Magdeburg
Germany	Studienpraxis Urologie	Nürtingen
Hungary	National Institute of Oncology	Budapest
Hungary	Bacs- Kiskun Megyei Korhaz	Kecskemét
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IRCCS - Istituto Europeo di Oncologia IEO	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio	Sondrio
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Marys Hospital Catholic University of Korea	Seoul
Korea, Republic of	Yonsei University Health System	Seoul
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego	Lublin
Poland	Med-Polonia Sp. z o. o.	Poznan
Poland	Szpital Grochowski im. dr med. Rafala Masztaka Sp. z o.o., 04-073, Warszawa, Poland	Warszawa
Poland	Mazowiecki Szpital Onkologiczny	Wieliszew
Spain	Hospital del Mar	Barcelona
Spain	ICO Hospitalet	Barcelona
Spain	IOB - Hospital Quiron Salud	Barcelona
Spain	Vall d Hebron Hospital	Barcelona
Spain	Hospital Universitario HM Sanchinarro CIOCC	Madrid
Spain	Marques de Valdecilla University Hospital	Santander
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Lausanne University Hospital	Lausanne
Switzerland	UniversitaetsSpital Zuerich	Zürich
United Kingdom	Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)	London
United Kingdom	The Sarah Cannon Research Institute	London
United Kingdom	University College London Hospitals	London
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	University of Texas Southwestern Medical Center (UTSWMC)	Dallas	Texas
United States	MD Anderson	Houston	Texas
United States	Englander Institute Weill Cornell Medicine	New York	New York
United States	CTCA Clinical Research Inc., Atlanta	Newnan	Georgia
United States	New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	NEXT Oncology	San Antonio	Texas
United States	Medical Oncology Associates PS (dba Summit Cancer Centers)	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Basilea Pharmaceutica

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)	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	From first dose up to 2 years
Primary	Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)	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	From first dose up to 2 years
Primary	Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2	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	From first dose up to 2 years
Secondary	Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies	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	From first dose up to 2 years
Secondary	Duration of Response (DOR) Per RECIST 1.1	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	From first dose up to 2 years
Secondary	ORR Based on RECIST 1.1 (Substudy 2)	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	From first dose up to 2 years
Secondary	Progression-free Survival (PFS) by RECIST in All Substudies	PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first	From first dose up to 2 years
Secondary	Overall Survival (OS) in All Substudies	OS was calculated from the date of cohort assignment until death from any cause	From first dose up to 2 years
Secondary	Number of Patients With at Least Grade 3 Adverse Events (AEs)	Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 )	From first dose and until 90 days following the last dose