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

Glioblastoma Clinical Trial

— FIGHT-209  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05267106
• Other study ID #: INCB 54828-209
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 20, 2022
• Est. completion date: November 29, 2024

Study information

• Verified date: January 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 83
• Est. completion date: November 29, 2024
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Glioblastoma
• Glioma
• Nervous System Neoplasms

Intervention

Drug:
• Pemigatinib
13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Overall Response Rate (ORR)	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).	Up to 3 months
Secondary	Cohort B : ORR	Defined as the proportion of participants who achieve a CR or PR based on RANO. Response will be determined by an ICR review.	up to 3 months
Secondary	Cohorts A and B combined: ORR	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.	Up to 3 months
Secondary	Cohorts A and B: Disease Control Rate (DCR)	Defined as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR in cohorts A and B respectively	Up to 3 months
Secondary	Cohorts A and B: Progression-Free Survival (PFS)	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	Up to 3 months
Secondary	Cohorts A and B: Overall Survival (OS)	Defined as the time from first dose of study drug to death due to any cause in cohorts A and B respectively	Up to 3 months
Secondary	Safety and tolerability	Safety and tolerability in each cohort, assessed by monitoring the frequency and severity of AEs according to NCICTCAE v5.0.	Up to 3 months
Secondary	Cohorts A and B : Duration Of Response (DOR)	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	up to 3 months