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)

Incyte

Status and phase: Active, not recruiting; Phase 2

Conditions: Glioblastoma; Adult-type Diffuse Gliomas

Treatments: Drug: Pemigatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05267106

INCB 54828-209

Details and patient eligibility

About

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.

Enrollment: 83 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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83 participants in 2 patient groups

Cohort A: IDH-wild-type GBM

Experimental group

Description:

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.

Treatment:

Drug: Pemigatinib

Cohort B: Other gliomas other than GBM

Experimental group

Description:

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

Treatment:

Drug: Pemigatinib