Clinical trial NCT04003610: Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)
Official title: A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisplatin-Ineligible Participants Whose Tumors Express FGFR3 Mutation or Rearrangement (FIGHT-205)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Urothelial Carcinoma
Unresectable Urothelial Carcinoma
Keywords: Urothelial carcinoma
fibroblast growth factor receptor (FGFR) inhibitor
FGFR3 mutation
FGFR3 rearrangement
metastatic
unresectable
cisplatin-ineligible
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2019-07-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of pemigatinib plus pembrolizumab or pemigatinib alone versus the standard of care for participants with metastatic or unresectable urothelial carcinoma who are not eligible to receive cisplatin, are harboring FGFR3 mutation or rearrangement, and who have not received prior treatment.


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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: up to 130 days
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 225 days
measure: Objective Response Rate (ORR)
timeFrame: up to 148 days
measure: Duration of Response (DOR)
timeFrame: up to 148 days
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: up to 178 days
measure: EORTC QLQ-C30 Score
timeFrame: up to 160 days
measure: Change From Baseline in the EORTC QLQ-C30 Score
timeFrame: Baseline; up to 160 days
measure: Number of Participants With the Indicated EQ-5D-5L Dimension Scores
timeFrame: up to 160 days
measure: Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score
timeFrame: Baseline; up to 160 days
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Newark
country: United States
facility: Christiana Care Helen F. Graham Cancer Center
state: Delaware
city: Marietta
country: United States
facility: Cotton-O'Neil Clinical Research Center, Hematology & Oncology
state: Georgia
city: Springfield
country: United States
facility: Simmons Cancer Institute At Siu
state: Illinois
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Biddeford
country: United States
facility: Smhc Cancer Blood Disorders
state: Maine
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Fort Worth
country: United States
facility: The Center For Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: Onc Consultants Pharmacy 2
state: Texas
city: Vienna
country: Austria
facility: Wilhelminenspital
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Moncton
country: Canada
facility: Moncton Hospital - Horizon Health Network
state: New Brunswick
city: Helsinki
country: Finland
facility: Helsinki University Meilahti Tower Hospital
city: Tampere
country: Finland
facility: Fonk Onkologian Klinikka
city: Turku
country: Finland
facility: Turku University Hospital, Sct Unit
city: Besancon
country: France
facility: Centre Hospitalier Universitaire de Besancon
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin Tripode
city: La Chaussee-saint-victor
country: France
facility: Polyclinique de Blois
city: Nimes
country: France
facility: Chu Nimes
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Cochin Cancerologie
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou (Hegp)
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Strasbourg
country: France
facility: Chu de Strasbourg Hopitaux Universitaires Service D Hematologie
city: Toulouse
country: France
facility: Institut Claudius Regaud Oncopole Toulouse
city: Moenchengladbach
country: Germany
facility: Kliniken Maria Hilf
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Bari
country: Italy
facility: Iov - Istituto Oncologico Veneto Irccs
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
city: Bologna
country: Italy
facility: L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA ï¿½ MALPIGHI
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
city: Milano
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Milano
country: Italy
facility: Ieo Istituto Europeo Di Oncologia Irccs
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Irccs G. Pascale
city: Roma
country: Italy
facility: UNIVERSITï¿½ CAMPUS BIO-MEDICO DI ROMA
city: Rozzano
country: Italy
facility: Irrcs Instituto Clinico Humanitas
city: Terni
country: Italy
facility: Azosp S.Maria Sc Oncologia
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Hirosaki-shi
country: Japan
facility: Hirosaki University Hospital
city: Hokkaido
country: Japan
facility: Hakodate Goryokaku Hospital
city: Hokkaido
country: Japan
facility: Sapporo Medical University Hospital
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
city: Kashihara-shi
country: Japan
facility: Nara Medical University Hospital
city: Kawasaki-shi
country: Japan
facility: St. Marianna University School of Medicine Hospital
city: Kita-gun
country: Japan
facility: Kagawa University Hospital
city: Matsuyama
country: Japan
facility: Nho Shikoku Cancer Center
city: Minato-ku
country: Japan
facility: Toranomon Hospital
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Saitama-shi
country: Japan
facility: Saitama Medical Center Jichi Medical University
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Olsztyn
country: Poland
facility: Olsztynski Osrodek Onkologiczny Kopernik
city: Lisboa
country: Portugal
facility: Champalimaud Foundation - Champalimaud Centre For the Unknown (Champalimaud Cancer Center)
city: Constanta
country: Romania
facility: Spitalul Clinic Judetean de Urgenta 'Sf Apostol Andrei' Constanta
city: Zilina
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Zilina
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Barcelona
country: Spain
facility: Ico Institut Catala D Oncologia
city: Girona
country: Spain
facility: Ico Girona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Hm Sanchinarro
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Barts Health Nhs Trust - St Bartholomews Hospital
Study officials:
affiliation: Incyte Corporation
name: Luis Feliz Vinas, MD
role: STUDY_DIRECTOR
References: