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)

  • STATUS
    Recruiting
  • End date
    May 5, 2025
  • participants needed
    189
  • sponsor
    Incyte Corporation
Updated on 10 August 2022
measurable disease
karnofsky performance status
FGFR1
EGFR
temozolomide
astrocytoma
oligodendroglioma
recurrent tumor
TERT
ccnu

Summary

This is an open-label, monotherapy study of pemigatinib in participants with recurrent glioblatoma (GBM) or other primary CNS tumors with an activating FGFR1-3 mutation or fusion/rearrangement. This study consists of 3 cohorts, Cohorts A, B, and C, and will enroll approximately 82, 82, and 25 participants into each cohort, respectively. 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.

Details
Condition Glioblastoma, Adult-type Diffuse Gliomas
Treatment pemigatinib
Clinical Study IdentifierNCT05267106
SponsorIncyte Corporation
Last Modified on10 August 2022

Eligibility

Yes No Not Sure

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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note