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

NCT05267106 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: INCB 54828-2092021-004740-24
• Study Type: interventional
• Target: 83
• Locations: 9 countries
• Sites: 79

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.

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in Participants With Recurrent Glioblastoma Based on Independent Central Review

  ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an independent centralized radiological review committee. CR requires all of the following: disappearance of all enhancing measurable/nonmeasurable disease sustained for ≥4 weeks; no new lesions; stable/improved nonenhancing lesions; off corticosteroids/on physiologic replacement doses only and stable/improved clinically. PR requires all of the following: ≥50% decrease, compared with baseline, in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for ≥4 weeks; no progression of nonmeasurable disease; no new lesions; stable or improved nonenhancing lesions on same/lower dose of corticosteroids compared with baseline scan; on a corticosteroid dose not greater than the dose at time of baseline scan and stable/improved clinically.

  up to 651 days

Secondary Outcomes (10)

• ORR in Participants With Recurrent Non-glioblastoma Central Nervous System Tumors Based on Independent Central Review

  up to 784 days

• Duration of Confirmed Response Based on Independent Central Review

  up to 784 days

• Duration of Unconfirmed Response Based on Independent Central Review

  up to 784 days

• ORR as Determined by Investigator Assessment

  up to 784 days

• Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

  up to 814 days

Study Arms (2)

Cohort A: IDH-wild-type GBM

EXPERIMENTAL

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.

Drug: Pemigatinib

Cohort B: Other gliomas other than GBM

EXPERIMENTAL

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

Drug: Pemigatinib

Interventions

Pemigatinib DRUG

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

Also known as: NCB054828

Cohort A: IDH-wild-type GBM; Cohort B: Other gliomas other than GBM

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (79)

Valkyrie Clinical Trials

Beverly Hills, California, 90211, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Providence Medical Foundation

Fullerton, California, 92835, United States

Location

Usc Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford Neuroscience Health Center

Sacramento, California, 94304, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Providence St Joseph Hospital Orange Center For Cancer Prevention and Treatment

Santa Monica, California, 90404, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510-3220, United States

Location

Baptist Md Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Orlando Health Cancer Institute Downtown Orlando

Orlando, Florida, 32806, United States

Location

H. Lee Moffitt Cancer Center and Research Institute Hospital

Tampa, Florida, 33612, United States

Location

University of Illinois Hospital & Health Sciences System

Chicago, Illinois, 60612, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

University of Minnesota Health Clinics and Surgery Center

Minneapolis, Minnesota, 55455, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

UC Health At Cincinnati Va Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37403, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Aalborg Universitets Hospital

Aalborg, 09000, Denmark

Location

Rigshospitalet Uni of Hospital of Copenhagen

Copenhagen, 02100, Denmark

Location

Odense University Hospital

Odense C, 05000, Denmark

Location

Chru de Lille Hopital Claude Huriez

Lille, 59037, France

Location

Chu Hopital de La Timone

Marseille, 13005, France

Location

Hospital Universitaire Pitie-Salpetriere

Paris, 75013, France

Location

Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole

Toulouse, 31059, France

Location

Universitatsklinikum Bonn Aoer

Bonn, 53127, Germany

Location

Klinikum Der Johann Wolfgang Goethe University

Frankfurt, 60528, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Tuebingen

Tübingen, 72076, Germany

Location

Ospedale Bellaria

Bologna, 40139, Italy

Location

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele

Milan, 20132, Italy

Location

Iov - Istituto Oncologico Veneto Irccs

Padua, 35128, Italy

Location

A.S.L. Napoli 1 Centro Ospedale Del Mare

Ponticelli, 80147, Italy

Location

Irccs Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza

Torino, 10124, Italy

Location

University of Tokyo Hospital

Bunkyō City, 113-8655, Japan

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Nagoya University Hospital

Nagoya, 466-8560, Japan

Location

Tohoku University Hospital

Sendai, 980-8574, Japan

Location

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Mc Cancer Institute

Rotterdam, 3015 GD, Netherlands

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Hospital General Universitario Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona Main

Barcelona, 08036, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Ico Girona Hospital Universitari de Girona Dr Josep Trueta

Girona, 17007, Spain

Location

Ico Institut Catala D Oncologia

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Hm Sanchinarro

Madrid, 28050, Spain

Location

Clinica Universidad de Navarra (Cun)

Pamplona, 31008, Spain

Location

Hospital General de Catalunya

Sant Cugat del Vallès, 08190, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Addenbrooke'S Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

St James'S University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust - Sutton

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust - Chelsea

London, SW36JJ, United Kingdom

Location

The Christie Nhs Foundation Trust Uk

Manchester, M20 4BX, United Kingdom

Location

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Oligodendroglioma; Central Nervous System Neoplasms

Interventions

pemigatinib

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Limitations and Caveats

The study was terminated by the sponsor after the prespecified interim analysis did not meet the futility boundary.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Victoria Ebiana, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 4, 2022
• Study Start: May 20, 2022
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: December 30, 2025
• Results First Posted: December 30, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.

Locations

US (32); DK (3); JP (6); FR (4); NL (2); ES (14); DE (4); IT (6); GB (8)