Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)

A Phase II Basket Study of the Oral Selective Pan-FGFR Inhibitor Debio 1347 in Subjects With Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3

The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Debio 1347

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Bowral, Australia, NSW 2576
    • Southern Highlands Private Hospital
  • Frankston, Australia, 3199
    • Peninsula and Southeast Oncology (PASO)
  • Nedlands, Australia, 6009
    • Linear Clinical Research, B Block Sir Charles Gairdner Hospital
  • Tugun, Australia, 4224
    • John Flynn Private Hospital
• Austria
  • Salzburg, Austria, 5020
    • LKH - Universitätsklinikum der PMU Salzburg
  • Wiener Neustadt, Austria, 2700
    • Landesklinikum Wiener Neustadt
• Brazil
  • Ijuí, Brazil, 98700-000
    • Hospital de Caridade de Ijuí, Avenida David J Martins
  • Rio Grande, Brazil, 90035-903
    • Hospital de Clinicas de Porto Alegre
  • Santo André, Brazil, 09060-870
    • Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia
  • São Paulo, Brazil, 01246-000
    • ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira, Avenida Doutor Arnaldo
• Bulgaria
  • Dobrich, Bulgaria, 9300
    • MHAT - Dobrich
  • Plovdiv, Bulgaria, 4004
    • Complex Oncological Center - Plovdiv, EOOD
  • Sofia, Bulgaria, 1632
    • MHAT "Serdika", EOOD
• Croatia
  • Varaždin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • University Hospital Centre, Sestre Milosrdnice
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni Nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni Nemocnice Olomouc
  • Prague, Czechia, 14000
    • Thomayerova nemocnice
  • Praha, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
• Denmark
  • Aalborg, Denmark, 9100
    • Ålborg Universitets Hospital
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital
  • Helsinki, Finland, 00180
    • Docrates Syöpäsairaala
• France
  • Angers, France, 49055
    • ICO - Site Paul Papin
  • Bordeaux, France, 33075
    • CHU Bordeaux - Hôpital Saint André, Groupe Hospitalier Sud - Hôpital Haut-Lévêque
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Pessac, France, 33604
    • Groupe Hospitalier Sud - Hôpital Haut Lévêque
  • Saint-Herblain, France, 44805
    • ICO - Site René Gauducheau
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens Laiko
  • Athens, Greece, 11528
    • General Hospital of Athens "Alexandra"
  • Athens, Greece, 11527
    • General Hospital of Athens of Chest Diseases "SOTIRIA"
  • Ioánnina, Greece, 45500
    • University General Hospital of Ioannina
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 13605
    • Seoul National University Bundang Hospital, Department of Oncology Medical office
  • Gyeonggi-do, Korea, Republic of
    • The Catholic University of Korea, St. Vincent's Hospital, CRC Room, 3F
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center, CRC Room, 18F, Artificial intelligence hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital (SNUH)
  • Suwon, Korea, Republic of, 16499
    • Ajou University Hospital, CRC room, Clinical Trial Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Den Haag, Netherlands, 2545 AA
    • Haga ziekenhuis
• Norway
  • Lørenskog, Norway, 1478
    • Akershus University Hospital
  • Oslo, Norway, 0310
    • Radiumhospitalet, Montebello
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctors' University Hospital (CDUH), Research Office
  • Ermita, Philippines, 1000
    • Philippine General Hospital, Clinical Trial Unit Room 5, Medical Research Laboratory
  • Quezon City, Philippines, 1112
    • St. Luke's Medical Center, Human Cancer Biobank Research Center
• Poland
  • Poznań, Poland, 60-355
    • Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
  • Warszawa, Poland, 02-106
    • MTZ Clinical Research
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
• Romania
  • Bucuresti, Romania, 014142
    • S.C Delta Health Care S.R.L
  • Cluj-Napoca, Romania, 400641
    • S.C Medisprof S.R.L.
  • Craiova, Romania, 200347
    • S.C Centrul de Oncologie Sf. Nectarie S.R.L.
  • Timişoara, Romania, 300166
    • S.C Oncocenter Oncologie Clinica S.R.L.
• Russian Federation
  • Arkhangel'sk, Russian Federation, 163045
    • SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
  • Barnaul, Russian Federation, 656049
    • TSBHI "Altai Territorial oncological dispensary"
  • Chelyabinsk, Russian Federation, 454048
    • LLC Evimed
  • Moscow, Russian Federation, 115478
    • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  • Omsk, Russian Federation, 644013
    • BHI of Omsk region "Clinical oncology dispensary"
  • Tomsk, Russian Federation, 634028
    • Tomsk Research Instutite of Oncology
• Singapore
  • Singapore, Singapore, 169610
    • Singapore National Cancer Center (SNCC)
  • Singapore, Singapore, 308440
    • Tan Tock Seng Hospital, Communicable Disease Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
• Taiwan
  • New Taipei City, Taiwan, 23561
    • Shuang Ho Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital, The Radiation Oncology Department
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11031
    • Taipei Medical University Hospital (TMUH)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital, Medical Science & Technology Building
  • Taoyuan, Taiwan, 33305
    • Linkou Chang-Gung Memorial Hospital
• Ukraine
  • Dnipro, Ukraine, 49102
    • CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
  • Kharkiv, Ukraine, 61070
    • Communal Non-profit Enterprise Regional Center of Oncology
  • Kharkiv, Ukraine, 61018
    • SI V.T. Zaycev Institute of general & urgent surgery of National academy medical sciences of Ukraine, Department of purulent surgery
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Ninewells Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SE1 9RY
    • Guy's Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Ironwood Cancer & Research Centers - Scottsdale
    • Tucson, Arizona, United States, 85721
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • Moores UCSD Cancer Center
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
  • Kentucky
    • Louisville, Kentucky, United States, 10202
      • James Graham Brown Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70122
      • Tulane University Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Cancer Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • UC Health, LLC.
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center - James Cancer Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • CTCA Cancer Treatment Centers
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn - Allegheny Oncology Network
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Hospitals & Clinics
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson/Seattle Care Alliance
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Cytologically or histologically confirmed advanced solid tumor
• Radiographic progression on prior systemic therapy; prior localized therapy (i.e., radiation, ablation, embolization) is allowed provided radiographic progression out-of-field or in the treatment, field is shown
• Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3 gene fusion/rearrangement potentially leading to a functional FGFR aberrant protein, identified through local and/or central molecular assay

Exclusion Criteria:

• History of hypersensitivity to any of the excipients in the Debio 1347 formulation
• History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular or cartilage/tendon calcifications
• Administration of any investigational agent within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Debio 1347 (Biliary Tract Cancer); Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks).	Drug: Debio 1347; Debio 1347 oral tablets.
Experimental: Cohort 2: Debio 1347 (Urothelial Cancer); Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks).	Drug: Debio 1347; Debio 1347 oral tablets.
Experimental: Cohort 3: Debio 1347 (All Other Solid Tumor Histologies); Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).	Drug: Debio 1347; Debio 1347 oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria	ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to disease progression or end of study (up to 1 year and 9 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC)	DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to disease progression or end of study (up to 2 years and 9 months)
Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC)	DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Up to disease progression or end of study (up to 2 years and 9 months)
Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC)	PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.	From the start of the study up to disease progression or death (up to 2 years and 9 months)
Overall Survival (OS)	OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.	Until death or loss to follow-up or end of study (up to 2 years and 9 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months)
Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma	Geometric mean and geometric percent CV summary was estimated based on log-linear model.	Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma	Geometric mean and geometric percent CV summary was estimated based on log-linear model.	Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)
Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)		Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2 (each cycle length = 28 days)

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Collaborators: Caris Life Sciences; Optimal Research (Just In Time sites)

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): January 4, 2022

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 7, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: Debio 1347-201; 2018-003584-53 (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