Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF302)

Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of infigratinib (an oral targeted FGFR1-3 inhibitor) versus placebo, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized 1:1 between infigratinib or placebo with treatment up to 1 year or until invasive local, distal, or metastatic disease recurrence confirmed by independent imaging reviewer.

Study Overview

• Status: Terminated
• Conditions: Upper Tract Urothelial Carcinomas; Urothelial Bladder Cancer
• Intervention / Treatment: Drug: Infigratinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • ZNA Middelheim
  • Brussel, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Leuven, Belgium
    • Universitair Ziekenhuis Leuven
  • Liège/Belgium
    • Liège, Liège/Belgium, Belgium, 4000
      • CHU de Liège - Sart Tilman
• Bulgaria
  • Burgas, Bulgaria, 8001
    • University Multiprofile Hospital For Active Treatment Deva Maria
  • Pleven, Bulgaria
    • University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
  • Sofia, Bulgaria
    • Multiprofile Hospital For Active Treatment "Sveta Sofia"
• Canada
  • Québec, Canada, G1R 2J6
    • Chu de Quebec Universite Laval
  • Vancouver, Canada
    • BC Cancer - Vancouver
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer- Vancouver
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre (MUHC)
• France
  • Brest, France, 29200
    • Hopital Morvan
  • Nantes, France
    • CHU de Nantes Hopital Hotel Dieu
  • Paris, France
    • Hopital Bichat - Claude - Bernard
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Saint-Grégoire, France, 35760
    • Centre Hospitalier Prive Saint-Gregoire
  • Saint-Herblain, France
    • Institut De Cancerologie De L'ouest - Site Saint-Herblain
  • Saint-Nazaire, France, 44600
    • Clinique Mutualiste de l'Estuaire
  • Villejuif, France
    • Gustave Roussy
  • Ile-de-France
    • Paris, Ile-de-France, France, 75013
      • Hopital Universitaire Pitie Salpetriere
    • Paris, Ile-de-France, France, 75015
      • Hopital Europeen Georges-Pompidou
  • Paris/France
    • Paris, Paris/France, France, 75018
      • CHU de Nantes Hopital Hotel Dieu
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69008
      • Centre de Lutte Contre le Cancer - Centre Léon Bérard
  • Strasbourg/France
    • Strasbourg, Strasbourg/France, France, 67200
      • Institut de cancerologie Strasbourg Europe
  • Toulouse/France
    • Toulouse, Toulouse/France, France, 31059
      • Institut Claudius Regaud
  • Villejuif/France
    • Villejuif, Villejuif/France, France, 94805
      • Gustave Roussy
• Germany
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin
  • Berlin, Germany
    • Urologie
  • Duesseldorf, Germany
    • University Hospital Duesseldorf
  • Homburg, Germany
    • Universitätsklinikum des Saarlandes Klinik für Urologie & Kinderurologie
  • Homburg/saar, Germany
    • Universitätsklinikum des Saarlandes Klinik für Urologie & Kinderurologie
  • Magdeburg, Germany
    • Universitätsklinikum Magdeburg
  • Regensburg, Germany, 93053
    • Caritas-Krankenhaus St. Josef Klinik für Urologie
  • Tübingen, Germany
    • Universitatsklinikum Tubingen
  • Berlin/Germany
    • Berlin, Berlin/Germany, Germany, 10117
      • Charité - Universitätsmedizin Berlin
  • Nordrhein-WestFalen
    • Duisburg, Nordrhein-WestFalen, Germany, 47179
      • Urologicum Duisburg
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40225
      • Universitätsklinikum Düsseldorf
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Universitatsklinikum Essen
    • Herne, Nordrhein-Westfalen, Germany, 44625
      • Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum
• Greece
  • Volos, Greece
    • Anassa General Clinic
  • Attica
    • Athens, Attica, Greece, 11526
      • Henry Dunant Hospital Center
  • Makedonia
    • Thessaloníki, Makedonia, Greece, 54622
      • Bioclinic Thessalonikis
• Italy
  • Aviano, Italy
    • Centro di Riferimento Oncologico
  • Bari, Italy, 70124
    • Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
  • Bari, Italy
    • A.O.U.C. Polclinico di Bari U.O. Oncologia Medica Universitaria
  • Casalmaggiore, Italy
    • ASST Cremona
  • Genova, Italy
    • Ospedale Policlinico San Martino IRCCS
  • Meldola, Italy
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy
    • Istituto Europeo di Oncologia
  • Milan, Italy
    • Fondazione IRCCS INT Milano
  • Napoli, Italy
    • Int Pascale Napoli
  • Orbassano, Italy
    • Aou San Luigi Gonzaga
  • Pisa, Italy
    • Azienda Ospedaliero-Universitaria Pisana
  • Reggio Emilia, Italy
    • IRCCS di Reggio Emilia
  • Roma, Italy
    • Policlinico Universitario Campus Biomedico
  • Torino, Italy
    • Citta Della Salute e Della Scienz - Torino
  • Trento, Italy
    • Ospedale di Trento - Presidio Ospedaliero Santa Chiara
  • Volterra, Italy
    • IRCCS Centro di Riferimento Oncologico di Basilicata
  • Cremona/Italy
    • Cremona, Cremona/Italy, Italy, 26100
      • Ospedale di Cremona
  • Genova/Italy
    • Genova, Genova/Italy, Italy, 16132
      • Ospedale Policlinico San Martino
  • Meldola/Italy
    • Meldola, Meldola/Italy, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano/Italy
    • Milano, Milano/Italy, Italy, 20141
      • Istituto Europeo di Oncologia
  • Naples
    • Napoli, Naples, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
  • Pisa/italy
    • Pisa, Pisa/italy, Italy, 56126
      • Azienda Ospedaliero-Universitaria Pisana
  • Potenza
    • Rionero In Vulture, Potenza, Italy, 85028
      • IRCCS Centro di Riferimento Oncologico di Basilicata
  • Reggio Emilia/Italy
    • Reggio Emilia, Reggio Emilia/Italy, Italy, 42100
      • Arcispedale Santa Maria Nuova
  • Roma/Italy
    • Roma, Roma/Italy, Italy, 00128
      • Università Campus Bio-Medico di Roma
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
  • Trentino
    • Trento, Trentino, Italy, 38100
      • Ospedale di Trento - Presidio Ospedaliero Santa Chiara
• Netherlands
  • Amsterdam, Netherlands
    • The Netherlands Cancer Institute
  • Geleen, Netherlands
    • Zuyderland MC locatie Sittard
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6532 SZ
      • Canisius-Wilhelmina Ziekenhuis
• Spain
  • Barcelona, Spain
    • Hospital del Mar
  • Barcelona, Spain
    • Hospital de La Santa Creu i Sant Pau
  • Manresa, Spain
    • Althaia Xarxa Assistencial Universitària de Manresa
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Català d'Oncologia Badalona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Parc Taulí de Sabadell
  • Barcelona/Spain
    • Barcelona, Barcelona/Spain, Spain, 08003
      • VHIO
    • Barcelona, Barcelona/Spain, Spain, 08041
      • Sofia
    • Barcelona, Barcelona/Spain, Spain, 08908
      • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
  • Córdoba/Spain
    • Córdoba, Córdoba/Spain, Spain, 14004
      • Hospital Universitario Reina Sofía
  • Girona/Spain
    • Girona, Girona/Spain, Spain, 17007
      • Institut Català D'Oncologia Girona
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta Hierro-Majadahonda
  • Madrid/Spain
    • Madrid, Madrid/Spain, Spain, 28033
      • MD Anderson Cancer Center Madrid
    • Madrid, Madrid/Spain, Spain, 28034
      • Hospital Universitario Ramón y Cajal
    • Madrid, Madrid/Spain, Spain, 28040
      • Hospital Clinico San Carlos
    • Madrid, Madrid/Spain, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid/Spain, Spain, 28046
      • Hospital Universitario La Paz
    • Madrid, Madrid/Spain, Spain, 28050
      • Hospital Universitario HM Sanchinarro
  • Sevilla/Spain
    • Sevilla, Sevilla/Spain, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Toledo/Spain
    • Toledo, Toledo/Spain, Spain, 45005
      • Hospital Virgen De La Salud
  • València
    • Valencia, València, Spain, 46009
      • Fundacion Instituto Valenciano de Oncologia
• United Kingdom
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
  • Stevenage, United Kingdom
    • Lister Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Duarte, California, United States, 91010
      • City of Hope - Duarte
    • Loma Linda, California, United States, 92350
      • Loma Linda University Faculty Medical Clinics
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Hialeah, Florida, United States, 33016
      • Urological Research Network Corp
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Health Hollis Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60637
      • UChicago Medicine Duchossois Center for Advanced Medicine (DCAM) - Hyde Park
    • Lisle, Illinois, United States, 60532
      • DuPage Medical Group - Warrenville Road
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University/Southeastern Louisiana VA Health Care
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University- SLUCare Academic Pavilion
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
    • Saddle Brook, New Jersey, United States, 07663
      • New Jersey Urology - Saddle Brook
    • Voorhees, New Jersey, United States, 08043
      • New Jersey Urology
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center - Division of Urology
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals - Syracuse
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Cancer Center
    • Raleigh, North Carolina, United States, 27609
      • Accellacare-DuPage Medical Group
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Arlington, Ohio, United States, 43606
      • University of Toledo
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University College of Medicine
    • Toledo, Ohio, United States, 43614
      • The University of Toledo Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Dallas, Texas, United States, 75390
      • Harold C. Simmons Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Bayor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital- Department of Urology
    • Richardson, Texas, United States, 75080
      • UT Southwestern
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute and Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria

1. Are randomized within 120 days following nephroureterectomy, distal ureterectomy or cystectomy.

2. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations. Variant histology is allowed provided urothelial carcinoma is predominant (>50%). Neuroendocrine (including small and large cell), sarcomatoid, and plasmacytoid variants are excluded (any component).

   1. Regarding samples and documentation of FGFR3

      • i. FGFR3 mutation is confirmed if: FGFR3 gene is mutated in Exon 7 (R248C, S249C), Exon 10 (G370C, A391E, Y373C), or Exon 15 (K650M/T, K650E/Q)

      OR

      • ii. FGFR3 gene fusion or FGFR3 rearrangement is confirmed based on the following genomic criteria if:

        • Any fusion/rearrangement with a literature-derived known partner gene regardless of strand or frame.
        • Fusion/rearrangements in the same strand that are in frame with a novel partner gene.
        • Fusion/rearrangements with one breakpoint in the intron 17 - exon 18 hotspot region and the other breakpoint in an intergenic region or another gene. This rule excludes 3' duplications comprising only exon 18.
      • iii. The amino acid numbers for the FGFR3 mutations refer to the functional FGFR3 isoform 1 (NP_000133.1) that is the NCBI Refseq ID used to report genetic alterations in FGFR3 by the FoundationOne® CDx test (F1CDx, Foundation Medicine, USA).

      • iv. FGFR3 alteration must be confirmed by Foundation Medicine for F1CDx testing:

        • The tumor sample to be used should be from the definitive surgical resection (cystectomy, nephroureterectomy, or distal ureterectomy), or from an archival biopsy of confirmed invasive urothelial carcinoma (≥pT2).
   2. If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be Stage ≥ ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Subjects who received less than this or non-cisplatin-based neoadjuvant treatment are not excluded.
   3. If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky criteria:
   4. Subjects who refuse cisplatin-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy based on Galsky criteria must also meet the following criteria:
   5. Must have a centrally reviewed negative postoperative computed tomography (CT) (defined as lymph nodes with short axis <1.0 cm and without growth and no distant metastases according to [RECIST v1.1 criteria or negative biopsy within 28 days before randomization to confirm absence of disease at baseline.
3. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
4. If a woman of childbearing potential, must have a negative pregnancy test within 7 days of the first dose of study drug. Sexually active males must use a condom during intercourse while taking study drug and for 1 month after the last dose of study drug and should not father a child during this period

Key Exclusion Criteria:

1. Presence of positive invasive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. In subjects not eligible for further surgery, radiotherapy, or other efficacious treatment, microscopic positive noninvasive margins (eg, carcinoma in situ) without gross residual disease are allowed.
2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.

3. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Prior anticancer or other therapies are restricted as follows:

   1. Prior adjuvant treatment for urothelial cancer is not allowed.
   2. Prior neoadjuvant therapy (eg, chemotherapy, immunotherapy, or investigational) is allowed if inclusion criterion #4 is met. Prior neoadjuvant chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug.
   3. Prior biologic, immunotherapy, or investigational therapy should have been completed within a period that is ≥5 half-lives or 30 days, whichever is shorter, before the first dose of study drug.
4. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
5. Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with medical monitor approval.
6. Have current evidence of corneal keratopathy or retinal disorder confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
7. Have a history and/or current evidence of extensive tissue calcification
8. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
9. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
10. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, or Seville oranges or products containing juice of these fruits within 7 days before the first dose of study drug; have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.

11. Have insufficient bone marrow function:

    1. Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L).
    2. Platelets <75,000/mm3 (<75 × 109/L).
    3. Hemoglobin <8.5 g/dL; transfusion support is allowed if >1 week before randomization and hemoglobin remains stable.

12. Have insufficient hepatic and renal function:

    1. Total bilirubin >1.5 × upper limit of normal (ULN) of the testing laboratory (for subjects with documented Gilbert syndrome, direct bilirubin must be ≤1.5 × ULN and enrollment requires approval by the medical monitor).
    2. AST/SGOT and ALT/SGPT >2.5 × ULN of the testing laboratory.
    3. Serum creatinine >1.5 × ULN or a calculated or measured creatinine clearance of <30 mL/min.
13. Have amylase or lipase >2.0 × ULN.

14. Have abnormal calcium or phosphorus:

    1. Inorganic phosphorus higher than 1.02 × ULN of the testing laboratory.
    2. Total serum calcium (can be corrected) higher than 1.02 × ULN of the testing laboratory.

15. Have clinically significant cardiac disease including any of the following:

    1. New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification.
    2. Uncontrolled hypertension
    3. Presence of CTCAE v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality.
    4. Unstable angina pectoris or acute myocardial infarction ≤3 months before the first dose of study drug.
    5. Average QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first ECG, a total of 3 ECGs separated by ≥5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard.
    6. History of congenital long QT syndrome.
16. Have had a recent (≤3 months before the first dose of study drug) transient ischemic attack or stroke.
17. If female, are pregnant or nursing (lactating).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infigratinib 125 mg; Participants will be randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks	Drug: Infigratinib; Participants randomly assigned to infigratinib will receive hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.; Other Names: Study drug; IP
Placebo Comparator: Placebo; Participants will be randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks	Drug: Placebo; Participants randomly assigned to placebo will receive placebo matching in appearance the investigational product (infigratinib), which will be provided as hard gelatin capsules for oral use and will be administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Centrally Determined Disease-free Survival (DFS)	DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, results will focus primarily on the primary and key secondary endpoints of the study. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.	The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed DFS	DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.	The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.
Metastasis-free Survival (MFS)	MFS was defined as the time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause, whichever occurred earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.	The time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause.
Overall Survival (OS)	Overall survival time was defined as the number of months from randomization to death. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.	The number of months from randomization to death.
Investigator-reviewed DFS Including Intraluminal Low-Risk Recurrence	Investigator assessment of intraluminal low-risk recurrence as assessed by DFS. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.	The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.
Number of Participants With Adverse Events (AEs)	Number of participants with AEs	From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm).
Number of Participants With Serious Adverse Events (SAEs)	Number of Participants with SAEs	From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm)

Collaborators and Investigators

• Sponsor: QED Therapeutics, Inc.
• Collaborators: Helsinn Healthcare SA
• Investigators: Study Director: David van Veenhuyzen, M.B., Ch.B., M.Pharm.Med., QED Therapeutics, Inc.

Publications and helpful links

General Publications

• Pal SK, Somford DM, Grivas P, Sridhar SS, Gupta S, Bellmunt J, Sonpavde G, Fleming MT, Lerner SP, Loriot Y, Hoffman-Censits J, Valderrama BP, Andresen C, Schnabel MJ, Cole S, Daneshmand S. Targeting FGFR3 alterations with adjuvant infigratinib in invasive urothelial carcinoma: the phase III PROOF 302 trial. Future Oncol. 2022 Jul;18(21):2599-2614. doi: 10.2217/fon-2021-1629. Epub 2022 May 24.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cystectomy; Adjuvant; Urothelial Bladder Cancer; UTUC; FGFR3; FGFR3 Genetic Alterations; Upper Tract Urothelial Carcinomas; Muscle Invasive Urothelial Carcinoma; Fibroblast Growth Factor Receptor Inhibitor; BGJ398; UBC; Infigratinib Phosphate; Infigratinib; Nephroureterectomy; Distal ureterectomy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Antineoplastic Agents; Infigratinib
• Other Study ID Numbers: QBGJ398-302; 2019-003248-63 (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