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
- Registration Number
- NCT05267106
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
-
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.
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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.
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MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit.
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: IDH-wild-type GBM Pemigatinib Participants with histopathologically proven, WHO Grade 4, IDH-wild-type GBM OR molecular diagnosis of IDH-wild-type, diffuse astrocytic glioma with molecular features of Grade 4 GBM that are recurrent, harboring FGFR1-3 fusions/or other rearrangements, or with a defined FGFR1-3 mutation or in-frame deletion. Cohort B: Other gliomas other than GBM Pemigatinib Participants with other histopathologically proven gliomas other than GBM, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors that are recurrent, harboring FGFR1-3 fusions/or other rearrangements or with a defined FGFR1-3 activating mutation or in-frame deletion
- Primary Outcome Measures
Name Time Method Cohort A: Overall Response Rate (ORR) Up to 3 months Defined as the proportion of participants in Cohort A who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an Independent Central Radiology (ICR).
- Secondary Outcome Measures
Name Time Method Cohorts A and B combined: ORR Up to 3 months Defined as the proportion of participants in Cohorts A and B who achieve a BOR of CR or PR based on RANO as determined by an ICR.
Cohorts A and B: Disease Control Rate (DCR) Up to 3 months Defined as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR in cohorts A and B respectively
Cohorts A and B: Progression-Free Survival (PFS) Up to 3 months Defined as the time from first dose until progressive disease (according to RANO and assessed by an ICR) or death (whichever occurs first) in cohorts A and B, respectively
Cohorts A and B: Overall Survival (OS) Up to 3 months Defined as the time from first dose of study drug to death due to any cause in cohorts A and B respectively
Safety and tolerability Up to 3 months Safety and tolerability in each cohort, assessed by monitoring the frequency and severity of AEs according to NCICTCAE v5.0.
Cohorts A and B : Duration Of Response (DOR) up to 3 months Defined as the time from first assessment of Complete Response (CR) or Partial Response (PR) until progressive disease (according to RANO and assessed by an ICR), or death (whichever occurs first) in cohorts A and B, respectively
Cohort B : ORR up to 3 months Defined as the proportion of participants who achieve a CR or PR based on RANO. Response will be determined by an ICR review.
Trial Locations
- Locations (78)
Providence Medical Foundation
🇺🇸Fullerton, California, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
University of Illinois Hospital & Health Sciences System
🇺🇸Chicago, Illinois, United States
University of Pittsburgh Medical Center Health System
🇺🇸Pittsburgh, Pennsylvania, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
UC Health At Cincinnati Va Medical Center
🇺🇸Cincinnati, Ohio, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Odense University Hospital
🇩🇰Odense C, Denmark
Valkyrie Clinical Trials
🇺🇸Beverly Hills, California, United States
Providence St Joseph Hospital Orange Center For Cancer Prevention and Treatment
🇺🇸Santa Monica, California, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Aalborg Universitets Hospital
🇩🇰Aalborg, Denmark
Chru de Lille Hopital Claude Huriez
🇫🇷Lille Cedex, France
Rigshospitalet Uni of Hospital of Copenhagen
🇩🇰Copenhagen, Denmark
Hospital Universitaire Pitie-Salpetriere
🇫🇷Paris, France
Chu Hopital de La Timone
🇫🇷Marseille, France
Universitatsklinikum Bonn Aoer
🇩🇪Bonn, Germany
Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
🇫🇷Toulouse, France
Klinikum Der Johann Wolfgang Goethe University
🇩🇪Frankfurt, Germany
University Hospital Tuebingen
🇩🇪Tuebingen, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Ospedale Bellaria
🇮🇹Bologna, Italy
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
🇮🇹Milano, Italy
A.S.L. Napoli 1 Centro Ospedale Del Mare
🇮🇹Ponticelli, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Iov - Istituto Oncologico Veneto Irccs
🇮🇹Padova, Italy
University of Tokyo Hospital
🇯🇵Bunkyo-ku, Japan
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
🇮🇹Torino, Italy
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Japan
Nagoya University Hospital
🇯🇵Nagoya-shi, Japan
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic Barcelona Main
🇪🇸Barcelona, Spain
Ico Girona Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Ico Institut Catala D Oncologia
🇪🇸L'hospitalet de Llobregat, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Hm Sanchinarro
🇪🇸Madrid, Spain
Clinica Universidad de Navarra (Cun)
🇪🇸Pamplona, Spain
Hospital General de Catalunya
🇪🇸Sant Cugat Del Valles, Spain
Addenbrooke'S Hospital
🇬🇧Cambridge, United Kingdom
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
St James'S University Hospital
🇬🇧Leeds, United Kingdom
Guys Hospital
🇬🇧London, United Kingdom
The Royal Marsden Nhs Foundation Trust - Sutton
🇬🇧London, United Kingdom
The Royal Marsden Nhs Foundation Trust - Chelsea
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust Uk
🇬🇧Manchester, United Kingdom
The Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Usc Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Kyoto University Hospital
🇯🇵Kyoto-shi, Japan
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of Minnesota Health Clinics and Surgery Center
🇺🇸Minneapolis, Minnesota, United States
Baptist Md Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Tohoku University Hospital
🇯🇵Sendai-shi, Japan
Erasmus Mc Cancer Institute
🇳🇱Rotterdam, Netherlands
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Stanford Neuroscience Health Center
🇺🇸Sacramento, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Orlando Health Cancer Institute Downtown Orlando
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute Hospital
🇺🇸Tampa, Florida, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States