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)
- Conditions
- brain tumorGlioblastoma10029211
- Registration Number
- NL-OMON53632
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 8
1. Ability to comprehend and willingness to sign a written ICF for the
study. For Germany: Only participants who can provide their own consent are
able to participate in this clinical study.
2. Male and female participants aged 18 years or older at the time of signing
the ICF.
3. Histological, cytological, or molecular confirmation of recurrent GBM or
other gliomas, circumscribed astrocytic gliomas, and glioneuronal or neuronal
tumors that have recurred.
a. For Cohort A: Prior, 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 per WHO 2021 (astrocytic glioma
requires presence of either amplification of EGFR,whole chromosome 7 gain and
whole chromosome 10 loss, or TERT promoter mutation) that has recurred or
progressed on or after treatment with at least 1 line of standard-of-care
therapy.
b. For Cohort B: Prior, histopathologically proven, per WHO criteria,
gliomas other than GBM (eg, IDH-mutant astrocytoma, IDH-mutant and 1p/19q
codeleted oligodendroglioma), circumscribed astrocytic gliomas, and
glioneuronal and neuronal tumors that are recurrent or have 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).
4. Radiographically measurable disease (per RANO). 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.
5. Karnofsky performance status >= 60.
6. Life expectancy >= 12 weeks.
7. Documentation of an actionable FGFR1-3 gene alteration (defined mutations,
gene fusion/rearrangements, or in-frame deletions) from tissue or cfDNA from a
qualified laboratory such as FMI or Guardant Health may be acceptable after
review by medical monitor. Participants with known FGFR resistance mutations
are not eligible.
a. Cohort A: 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 per WHO 2021 (astrocytic glioma
requires presence of either amplification of EGFR, whole chromosome 7 gain and
whole chromosome 10 loss, or TERT promoter mutation) that are recurrent,
harboring FGFR1-3 fusions/or other rearrangements (FGFR1-3 in-frame fusions,
any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner) or with a
defined FGFR1-3 activating mutation or in-frame deletion. Only participants
with FGFR fusions or rearrangements with an intact kinase domain are eligible.
b. Cohort B: Participants with other histopathologically proven, per WHO
criteria, gliomas other than GBM (eg, IDH-mutant astrocytoma, IDHmutant
and 1p/19q codeleted oligodendroglioma), circumscribed astrocytic gliomas, and
glioneuronal and neuronal tumors that are recurrent, harboring FGFR1-3
fusions/or other rearrangements (FGFR1-3 in-frame fusions, any FGFR2
rearrangement, FGFR1/3 rearrangement with known partner) or with a defined
FGFR1-3 activating mutation or in-frame deletion. Only FGFR fusions or
rearrangements with an intact kinase domain are eligible.
8. MRI-documented objective
1. Prior receipt of a selective an FGFR inhibitor.
2. 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) from AEs from previously
administered therapies.
3. Participants may have had treatment for an unlimited number of prior
relapses but must not have had prior bevacizumab or other VEGF/VEGFR inhibitors.
4. Concurrent anticancer therapy.
5. Candidate for potentially curative surgery.
6. Dexamethasone (or equivalent) > 4 mg daily at the time of study registration
(higher dose of steroid for symptom control is allowed during the study).
7. Current evidence of clinically significant corneal or retinal disorder as
confirmed by ophthalmologic examination.
8. Diffuse leptomeningeal disease.
9. 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.
10. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>ORR in Cohort A, defined as the proportion of participants in Cohort A who<br /><br>achieve a BOR of CR or PR based on RANO as determined by an ICR.</p><br>
- Secondary Outcome Measures
Name Time Method