Derazantinib and Atezolizumab in Patients With Urothelial Cancer (FIDES-02)

An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations

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.

Study Overview

• Status: Completed
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: Derazantinib 300 mg once daily monotherapy; Drug: Derazantinib 200 mg once daily + atezolizumab 1200 mg; Drug: Derazantinib 300 mg once daily+ atezolizumab 1200 mg; Drug: Derazantinib 200 mg twice daily + atezolizumab 1200 mg; Drug: Derazantinib 300 mg once daily monotherapy (QD); Drug: Derazantinib 300 mg once daily + atezolizumab 1200 mg; Drug: Derazantinib 200 mg twice daily monotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Birtinya, Australia, 4575
    • Coastal Cancer Care
  • Canberra, Australia, 2065
    • Canberra Hospital and Health Services
  • Tugun, Australia, 4224
    • John Flynn Private Hospital
  • Wendouree, Australia, 3355
    • Ballarat Oncology & Haematology Services
  • Westmead, Australia, 2145
    • Westmead Hospital
• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH) - Universitaetsklinik fuer Urologie
• Canada
  • Hamilton, Canada, L8V 5C2
    • Juravinski Cancer Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• Czechia
  • Brno, Czechia, 61700
    • Fakultni Nemocnice u sv. Anny v Brne
  • Olomouc, Czechia, 77900
    • Fakultní Nemocnice Olomouc
• France
  • Bordeaux, France, 33076 CEDEX
    • Institut Bergonié
  • Caen, France, 14000
    • Centre François Baclesse
  • Marseille, France, 13005
    • CHU Timone / CEPCM
  • Paris, France, 75030
    • Medical Oncology - Pitié-Salpêtrière Hopital
  • Toulouse, France, 31100
    • IUCT-Oncopole de Toulouse
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Campus Charite Mitte
  • Duesseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Erlangen, Germany, 91054
    • University Clinic Erlangen
  • Magdeburg, Germany, 39120
    • Universitaetsklinikum Magdeburg A.oe.R
  • Nürtingen, Germany, 72622
    • Studienpraxis Urologie
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology
  • Kecskemét, Hungary, 6000
    • Bacs- Kiskun Megyei Korhaz
• Italy
  • Milano, Italy, 20133
    • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20122
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
  • Milano, Italy, 20141
    • IRCCS - Istituto Europeo di Oncologia IEO
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
  • Sondrio, Italy, 23100
    • ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Daejeon, Korea, Republic of, 35105
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 3722
    • Yonsei University Health System
  • Seoul, Korea, Republic of, 6591
    • Seoul St. Marys Hospital Catholic University of Korea
• Poland
  • Lublin, Poland, 20-718
    • Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego
  • Poznań, Poland, 60-693
    • Med-Polonia Sp. z o. o.
  • Warszawa, Poland, 04-073
    • Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., 04-073, Warszawa, Poland
  • Wieliszew, Poland, 05-135
    • Mazowiecki Szpital Onkologiczny
• Spain
  • Barcelona, Spain, 8003
    • Hospital Del Mar
  • Barcelona, Spain, 08035
    • Vall d Hebron Hospital
  • Barcelona, Spain, 8023
    • IOB - Hospital Quiron Salud
  • Barcelona, Spain, 8908
    • ICO Hospitalet
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro CIOCC
  • Santander, Spain, 39011
    • Marqués de Valdecilla University Hospital
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Sevilla, Spain, 14009
    • Hospital Universitario Virgen Macarena
• Switzerland
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden
  • Lausanne, Switzerland, 1011
    • Lausanne University Hospital
  • Zürich, Switzerland, 8091
    • Universitaetsspital Zuerich
• United Kingdom
  • London, United Kingdom, W1T7HA
    • University College London Hospitals
  • London, United Kingdom, EC1M 6BQ
    • Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)
  • London, United Kingdom, W1G 6AD
    • The Sarah Cannon Research Institute
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
• United States
  • Georgia
    • Newnan, Georgia, United States, 30265
      • CTCA Clinical Research Inc., Atlanta
  • New York
    • New York, New York, United States, 10021
      • Englander Institute Weill Cornell Medicine
    • Port Jefferson Station, New York, United States, 11776
      • New York Cancer and Blood Specialists
  • Texas
    • Dallas, Texas, United States, 75390-8852
      • University of Texas Southwestern Medical Center (UTSWMC)
    • Houston, Texas, United States, 77030
      • MD Anderson
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates PS (dba Summit Cancer Centers)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1: Derazantinib 300 mg once daily; Patients with urothelial cancer were treated with derazantinib 300 mg once daily	Drug: Derazantinib 300 mg once daily monotherapy; Derazantinib was administered orally at a dose of 300 mg once daily
Experimental: Substudy 2 (Dose-Level 1): 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	Drug: 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
Experimental: Substudy 2 (Dose-Level 2): 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	Drug: 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
Experimental: Substudy 3: 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	Drug: 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
Experimental: Substudy 4 (Cohort 4a):Derazantinib 300 mg once daily; Patients with FGFR inhibitor resistant urothelial cancer were treated with derazantinib 300 mg once daily	Drug: Derazantinib 300 mg once daily monotherapy (QD); Derazantinib was administered orally at a dose of 300 mg once daily
Experimental: Substudy 4 (Cohort 4b):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	Drug: 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
Experimental: Substudy 5: Derazantinib 200 mg twice daily; Patients with urothelial cancer were treated with derazantinib 200 mg twice daily	Drug: Derazantinib 200 mg twice daily monotherapy; Derazantinib was administered orally at a dose of 200 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Manuel Häckl, MD, Basilea Pharmaceutica International Ltd, Allschwil

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2019
• Primary Completion (Actual): October 4, 2022
• Study Completion (Actual): October 4, 2022

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: bladder cancer; solid tumor; targeted therapy; atezolizumab; checkpoint inhibitor; Tecentriq; immune checkpoint blockade; FGFR genetic aberration; derazantinib; metastatic urothelial cancer; Fibroblast Growth Factor Receptor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: DZB-CS-201; 2019-000359-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No