Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)
Metastatic Urothelial Carcinoma, Unresectable Urothelial Carcinoma
About this trial
This is an interventional treatment trial for Metastatic Urothelial Carcinoma focused on measuring Urothelial carcinoma, fibroblast growth factor receptor (FGFR) inhibitor, FGFR3 mutation, FGFR3 rearrangement, metastatic, unresectable, cisplatin-ineligible
Eligibility Criteria
Inclusion Criteria:
- Histologically documented metastatic or unresectable urothelial carcinoma. Both transitional cell and mixed transitional cell histologies are allowed, provided urothelial component is ≥ 50%.
- At least 1 measurable target lesion per RECIST v1.1.
- Must be ineligible to receive cisplatin. Patients ineligible for any platinum-based chemotherapy are allowed.
- Known FGFR3 mutation or rearrangement confirmed by the central laboratory prior to randomization.
- Central laboratory test result of PD-L1 status is mandatory at screening.
- Have received no prior systemic chemotherapy for metastatic or unresectable urothelial carcinoma (except adjuvant platinum-based chemotherapy following radical cystectomy, with recurrence > 12 months from completion of therapy, or neo-adjuvant platinum-based chemotherapy, with recurrence > 12 months since completion of therapy).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
- Prior receipt of a selective FGFR inhibitor for any indication or reason.
- Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
- Receipt of anticancer medications or investigational drugs for unresectable and/or metastatic disease.
- Concurrent anticancer therapy, except for treatment allowed per protocol.
- Has disease that is suitable for local therapy administered with curative intent.
- Has tumor with any neuroendocrine or small cell component.
- Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
- Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment.
- Has central nervous system metastases, unless the participant has completed local therapy (eg, whole brain radiation therapy, surgery, radiosurgery) and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study.
- Known additional malignancy that is progressing or required active treatment within the past 3 years
- Laboratory values outside the protocol-defined range at screening.
- Clinically significant or uncontrolled cardiac disease.
- History of autoimmune disease that has required systemic treatment in past 2 years.
Sites / Locations
- Marin Cancer Care
- Christiana Care Helen F. Graham Cancer Center
- Cotton-O'Neil Clinical Research Center, Hematology & Oncology
- Simmons Cancer Institute At Siu
- The University of Kansas Cancer Center
- Smhc Cancer Blood Disorders
- Summit Medical Group
- Mount Sinai School of Medicine
- Oregon Health & Science University
- Charleston Hematology Oncology Associates
- Vanderbilt-Ingram Cancer Center
- The Center For Cancer and Blood Disorders
- Onc Consultants Pharmacy 2
- Wilhelminenspital
- Grand Hopital de Charleroi
- Universitaire Ziekenhuis Leuven - Gasthuisberg
- Moncton Hospital - Horizon Health Network
- Helsinki University Meilahti Tower Hospital
- Fonk Onkologian Klinikka
- Turku University Hospital, Sct Unit
- Centre Hospitalier Universitaire de Besancon
- Groupe Hospitalier Pellegrin Tripode
- Polyclinique de Blois
- Chu Nimes
- Groupe Hospitalier Pitie-Salpetriere
- Hopital Cochin Cancerologie
- Hopital Europeen Georges Pompidou (Hegp)
- Centre Hospitalier Universitaire de Poitiers
- Chu de Strasbourg Hopitaux Universitaires Service D Hematologie
- Institut Claudius Regaud Oncopole Toulouse
- Kliniken Maria Hilf
- University Hospital Waterford
- Iov - Istituto Oncologico Veneto Irccs
- Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
- L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
- Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
- Fondazione Irccs Istituto Nazionale Dei Tumori
- Ieo Istituto Europeo Di Oncologia Irccs
- Fondazione Irccs Ca Granda Ospedale Maggiore
- Istituto Nazionale Tumori Fondazione Irccs G. Pascale
- UNIVERSIT� CAMPUS BIO-MEDICO DI ROMA
- Irrcs Instituto Clinico Humanitas
- Azosp S.Maria Sc Oncologia
- Chiba University Hospital
- Chiba Cancer Center
- National Hospital Organization Kyushu Cancer Center
- Saitama Medical University International Medical Center
- Hirosaki University Hospital
- Hakodate Goryokaku Hospital
- Sapporo Medical University Hospital
- Nihon University Itabashi Hospital
- Nara Medical University Hospital
- St. Marianna University School of Medicine Hospital
- Kagawa University Hospital
- Nho Shikoku Cancer Center
- Toranomon Hospital
- Osaka International Cancer Institute
- Saitama Medical Center Jichi Medical University
- Tohoku University Hospital
- Jichi Medical University Hospital
- Keio University Hospital
- Osaka University Hospital
- National Cancer Center Hospital
- Toyama University Hospital
- Olsztynski Osrodek Onkologiczny Kopernik
- Champalimaud Foundation - Champalimaud Centre For the Unknown (Champalimaud Cancer Center)
- Spitalul Clinic Judetean de Urgenta 'Sf Apostol Andrei' Constanta
- Fakultna Nemocnica S Poliklinikou Zilina
- Hospital Clinic I Provincial
- Ico Institut Catala D Oncologia
- Ico Girona
- Hospital Clinico San Carlos
- Hospital Universitario 12 de Octubre
- Hospital Universitario de La Paz
- Hospital Universitario Hm Sanchinarro
- Hospital Puerta de Hierro
- Hospital Universitario Virgen Del Rocio
- Hospital Clinico Universitario de Valencia
- Barts Health Nhs Trust - St Bartholomews Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Pemigatinib + Pembrolizumab
Pemigatinib
Standard of Care
Combination of pemigatinib (13.5 milligrams [mg] once a day orally) plus pembrolizumab (200 mg every 3 weeks [Q3W] intravenously [IV])
Pemigatinib (13.5 mg once a day orally) alone
Either gemcitabine plus carboplatin or pembrolizumab as standard of care. Gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or 2 of each 3-week cycle. Pembrolizumab 200 mg IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.