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)
Glioblastoma, Adult-type Diffuse Gliomas
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
Histological, cytological, or molecular confirmation of recurrent GBM or other adult-type, diffuse glioma or circumscribed astrocytic tumors.
- For Cohorts A and C: Prior histopathologically proven WHO grade 4, IDH-wild-type GBM OR molecular diagnosis of IDH-wild-type, diffuse astrocytic glioma with molecular features of WHO grade 4 GBM (astrocytic glioma requires presence of either amplification of EGFR, whole chromosome 7 gain and whole chromosome 10 loss, or TERT-promoter mutation; Louis et al 2021) that has recurred or progressed on or after treatment with at least 1 line of standard of care therapy (eg, temozolomide and radiotherapy or radiotherapy).
- For Cohorts B and C: Prior histopathologically proven, per WHO criteria, adult-type diffuse gliomas other than GBM, including IDH-mutant astrocytoma and IDH-mutant and 1p/19q codeleted oligodendroglioma, and circumscribed astrocytic tumors, including pilocytic astrocytomas, that are recurrent or progressed on or after at least 1 line of standard of care therapy (eg, radiotherapy and/or treatment with an alkylating chemotherapy such as TMZ, CCNU, or BCNU-containing chemotherapy). For Cohort C, all gliomas and glioneuronal and neuronal tumors with a known or likely FGFR 1-3 activating mutation are also eligible.
- Radiographically measurable disease. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been clearly demonstrated in the lesion.
- Karnofsky performance status ≥ 60.
- Life expectancy ≥ 12 weeks.
Documentation of an FGFR1-3 gene mutation or fusion/rearrangement from tissue (cfDNA from a qualified laboratory such as FMI or Guardant Health may be acceptable after review by medical monitor).
- Cohort A: Participants with prior, histopathologically proven, WHO grade 4,IDH-wild-type GBM OR molecular diagnosis of IDH-wild-type, diffuse astrocytic glioma with molecular features of WHO grade 4 GBM (astrocytic glioma requires presence of either amplification of EGFR, whole chromosome 7 gain and whole chromosome 10 loss, or TERT-promoter mutation; Louis et al 2021) that has recurred, harboring FGFR1-3 fusions or rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner). Only FGFR fusions or rearrangements with an intact kinase domain are eligible.
- Cohort B: Participants with other histopathologically proven, per WHO criteria dult-type, diffuse gliomas other than GBM, including IDH-mutant astrocytoma and IDH-mutant and 1p/19q codeleted oligodendroglioma, and circumscribed astrocytic tumors, including pilocytic astrocytomas that are recurrent, harboring FGFR1-3 fusions or rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner). Only FGFR fusions or rearrangements with an intact kinase domain are eligible.
- Cohort C: Participants with prior, histopathologically proven, WHO grade 4, IDH-wild-type GBM or molecular diagnosis of IDH-wild-type, diffuse astrocytic glioma with molecular features of WHO grade 4 GBM that has recurred or histopathologically proven, per WHO criteria, adult-type, diffuse gliomas other than GBM, including IDH-mutant astrocytoma and IDH-mutant and 1p/19q codeleted oligodendroglioma, and circumscribed astrocytic tumors, including pilocytic astrocytomas, that are recurrent with a known or likely activating mutation or FGFR1-3 mutation. All gliomas and glioneuronal and neuronal tumors with a known or likely FGFR 1-3 activating mutation are also eligible.
- MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit. An interval of at least 12 weeks after prior radiotherapy is required unless there is either histopathological confirmation of recurrent tumor or new enhancement on MRI outside the radiotherapy field. Participants who are intolerant of or decline the approved therapy are eligible only if they have no therapy available that is likely to provide clinical benefit.
- Baseline archival tumor specimen less than 24 months from date of screening. 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 a selective FGFR inhibitor.
- Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of study drug. Participants must have recovered (≤ Grade 1 as per CTCAE v5.0 or at pretreatment baseline) from AEs from previously administered therapies (excluding alopecia).
- 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 (eg, chemotherapy, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
- Candidate for potentially curative surgery.
- Dexamethasone (or equivalent) > 4 mg daily at the time of study registration (higher doseof steroid for symptom control is allowed during the study).
- Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination.
- Diffuse leptomeningeal disease.
- Radiation therapy administered within 12 weeks before enrollment/first dose of study drug. An interval of at least 12 weeks after prior radiotherapy is required unless there is either histopathological confirmation of recurrent tumor or new enhancement on MRI outside the radiotherapy field.
- Known additional malignancy that is progressing or requires active systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin,or in situ cervical cancer that has undergone potentially curative therapy.
- Participants with defined laboratory values at screening.
Sites / Locations
- Valkyrie Clinical TrialsRecruiting
- City of Hope National Medical CenterRecruiting
- Providence Medical FoundationRecruiting
- Usc Norris Comprehensive Cancer CenterRecruiting
- Stanford Neuroscience Health CenterRecruiting
- Sharp Memorial HospitalRecruiting
- University of California San FranciscoRecruiting
- Providence St Joseph Hospital Orange Center For Cancer Prevention and TreatmentRecruiting
- Yale Cancer CenterRecruiting
- Baptist Md Anderson Cancer CenterRecruiting
- Miami Cancer InstituteRecruiting
- Orlando Health Cancer Institute Downtown Orlando
- Tampa General Hospital/University of South Florida
- H. Lee Moffitt Cancer Center and Research Institute HospitalRecruiting
- Rush University Medical Center-Consultants in Hematology
- University of Illinois Hospital & Health Sciences SystemRecruiting
- University of Iowa Hospital and ClinicsRecruiting
- University Medical Center New Orleans
- University of Minnesota Health Clinics and Surgery Center
- Washington University
- Northwell HealthRecruiting
- Columbia University Irving Medical CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- East Carolina UniversityRecruiting
- Wake Forest Baptist HealthRecruiting
- UC Health At Cincinnati Va Medical CenterRecruiting
- Cleveland Clinic FoundationRecruiting
- The Ohio State University
- Spoknwrd Clinical Trials Inc.
- University of Pennsylvania HospitalRecruiting
- University of Pittsburgh Medical Center Health SystemRecruiting
- Rhode Island Hospital
- Tennessee OncologyRecruiting
- Tennessee OncologyRecruiting
- Baylor University Medical CenterRecruiting
- Houston Methodist HospitalRecruiting
- Huntsman Cancer InstituteRecruiting
- Fred Hutchinson Cancer Research CenterRecruiting
- West Virginia University Cancer Institute
- Aalborg Universitets HospitalRecruiting
- Rigshospitalet Uni of Hospital of CopenhagenRecruiting
- Odense University HospitalRecruiting
- Chru de Lille Hopital Claude HuriezRecruiting
- Chu Hopital de La TimoneRecruiting
- Hospital Universitaire Pitie-SalpetriereRecruiting
- Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-OncopoleRecruiting
- Universitatsklinikum Bonn AoerRecruiting
- Klinikum Der Johann Wolfgang Goethe UniversityRecruiting
- Universitaetsklinikum HeidelbergRecruiting
- University Hospital Grosshadern Munich
- University Hospital TuebingenRecruiting
- Ospedale BellariaRecruiting
- Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San RaffaeleRecruiting
- Iov - Istituto Oncologico Veneto IrccsRecruiting
- A.S.L. Napoli 1 Centro Ospedale Del MareRecruiting
- Irccs Istituto Clinico HumanitasRecruiting
- Azienda Ospedaliero Universitaria Citta Della Salute E Della ScienzaRecruiting
- University of Tokyo HospitalRecruiting
- National Cancer Center HospitalRecruiting
- Kyushu University HospitalRecruiting
- Kyoto University HospitalRecruiting
- Nagoya University HospitalRecruiting
- Tohoku University HospitalRecruiting
- Netherlands Cancer Institute Antoni Van Leeuwenhoek ZiekenhuisRecruiting
- Erasmus Mc Cancer InstituteRecruiting
- Hospital Del MarRecruiting
- Hospital General Universitario Vall D HebronRecruiting
- Hospital Clinic Barcelona MainRecruiting
- Hospital de La Santa Creu I Sant PauRecruiting
- Ico Institut Catala D OncologiaRecruiting
- Ico Girona Hospital Universitari de Girona Dr Josep TruetaRecruiting
- Hospital General Universitario Gregorio MaranonRecruiting
- Hospital Universitario Ramon Y CajalRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital Universitario Hm SanchinarroRecruiting
- Clinica Universidad de Navarra (Cun)Recruiting
- Hospital General de CatalunyaRecruiting
- Hospital Universitario Virgen Del RocioRecruiting
- Hospital General Universitario de ValenciaRecruiting
- Addenbrooke'S HospitalRecruiting
- Velindre Cancer CentreRecruiting
- St James'S University HospitalRecruiting
- Guys HospitalRecruiting
- The Royal Marsden Nhs Foundation Trust - SuttonRecruiting
- The Royal Marsden Nhs Foundation Trust - ChelseaRecruiting
- The Christie Nhs Foundation Trust UkRecruiting
- The Clatterbridge Cancer Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort A: IDH-wild-type GBM
Cohort B: Other gliomas other than GBM
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.
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