Clinical trial NCT05267106: Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations
Official title: A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Adult-type Diffuse Gliomas
Keywords: glioblastoma
GBM
adult-type diffuse gliomas
gliomas
oligodendroglioma
FGFR1-3 Alteration
FGFR1-3 fusions
FGFR1-3 rearrangements
Central nervous system tumor
isocitrate dehydrogenase
IDH-mutant astocytoma
IDH-wild-type GBM
glioneuronal
neuronal
circumscribed astrocytic glioma
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2022-03-04
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study consists of 2 cohorts and participants will receive pemigatinib 13.5 mg QD on a 2-week on-therapy and 1-week off-therapy schedule.
Primary purpose: TREATMENT

Brief summary: This is an open-label, monotherapy study of pemigatinib in participants with recurrent glioblastoma (GBM) or other recurrent gliomas, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors with an activating FGFR1-3 mutation or fusion/rearrangement. This study consists of 2 cohorts, Cohorts A, and B, and will enroll approximately 82 participants into each cohort. Participants will receive pemigatinib 13.5 mg QD on a 2-week on-therapy and 1-week off-therapy schedule as long as they are receiving benefit and have not met any criteria for study withdrawal.


Eligibility criteria: Inclusion Criteria:

* Histological, cytological, or molecular confirmation of recurrent GBM or other glioma, circumscribed astrocytic glioma, or glioneuronalor neuronal tumors that has recurred.
* Radiographically measurable disease.

  . -Karnofsky performance status ≥ 60.
* Life expectancy ≥ 12 weeks.
* Documentation of an actionable FGFR1-3 gene mutation or fusion/rearrangement from tissue : FGFR1-3 fusions or other rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner) or a defined FGFR1-3 activating mutation or in-frame deletion. Only participants with FGFR fusions or rearrangements with an intact kinase domain are eligible.
* MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit.
* Most recent archival tumor specimen must be a tumor block or a minimum of 15 unstained slides from biopsy or resection of primary tumor or metastasis.
* Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

* Prior receipt of an FGFR inhibitor.
* Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of study drug.
* Participants may have had treatment for an unlimited number of prior relapses but must not have had prior bevacizumab or other VEGF/VEGFR inhibitors (exception: prior bevacizumab is allowed if it was administered for the treatment of radiation necrosis rather than progressive tumor and was stopped at least 12 weeks prior to MRI showing tumor progression).
* Concurrent anticancer therapy
* Candidate for potentially curative surgery.
* Dexamethasone (or equivalent) \> 4 mg daily at the time of study registration
* Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
* Diffuse leptomeningeal disease.
* Radiation therapy administered within 12 weeks before enrollment/first dose of study drug.
* Known additional malignancy that is progressing or requires active systemic treatment.

Primary outcomes:
measure: Cohort A: Overall Response Rate (ORR)
timeFrame: Up to 3 months
Secondary outcomes:
measure: Cohort B : ORR
timeFrame: up to 3 months
measure: Cohorts A and B combined: ORR
timeFrame: Up to 3 months
measure: Cohorts A and B: Disease Control Rate (DCR)
timeFrame: Up to 3 months
measure: Cohorts A and B: Progression-Free Survival (PFS)
timeFrame: Up to 3 months
measure: Cohorts A and B: Overall Survival (OS)
timeFrame: Up to 3 months
measure: Safety and tolerability
timeFrame: Up to 3 months
measure: Cohorts A and B : Duration Of Response (DOR)
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Monica
country: United States
facility: Providence St Joseph Hospital Orange Center For Cancer Prevention and Treatment
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Md Anderson Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute Downtown Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute Hospital
state: Florida
city: Chicago
country: United States
facility: University of Illinois Hospital & Health Sciences System
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Minneapolis
country: United States
facility: University of Minnesota Health Clinics and Surgery Center
state: Minnesota
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health At Cincinnati Va Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Aalborg
country: Denmark
facility: Aalborg Universitets Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet Uni of Hospital of Copenhagen
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Lille Cedex
country: France
facility: Chru de Lille Hopital Claude Huriez
city: Marseille
country: France
facility: Chu Hopital de La Timone
city: Paris
country: France
facility: Hospital Universitaire Pitie-Salpetriere
city: Toulouse
country: France
facility: Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn Aoer
city: Frankfurt
country: Germany
facility: Klinikum Der Johann Wolfgang Goethe University
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Milano
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
city: Padova
country: Italy
facility: Iov - Istituto Oncologico Veneto Irccs
city: Ponticelli
country: Italy
facility: A.S.L. Napoli 1 Centro Ospedale Del Mare
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
city: Bunkyo-ku
country: Japan
facility: University of Tokyo Hospital
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Mc Cancer Institute
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona Main
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Girona
country: Spain
facility: Ico Girona Hospital Universitari de Girona Dr Josep Trueta
city: L'hospitalet de Llobregat
country: Spain
facility: Ico Institut Catala D Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Hm Sanchinarro
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (Cun)
city: Sant Cugat Del Valles
country: Spain
facility: Hospital General de Catalunya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Cambridge
country: United Kingdom
facility: Addenbrooke'S Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Leeds
country: United Kingdom
facility: St James'S University Hospital
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Sutton
city: London
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Chelsea
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre
Study officials:
affiliation: Incyte Corporation
name: Victoria Ebiana, MD
role: STUDY_DIRECTOR
References: