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
- Male and female participants at least 18 years of age who have recurrent GBM or other recurrent primary CNS tumors harboring an FGFR1-3 rearrangement or fusion, who have progressed on at least one line of standard of care therapy, eg chemotherapy and/or radiation therapyMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-004740-24-DK
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 189
1. Ability to comprehend and willingness to sign a written ICF for the 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 adult type, diffuse glioma or circumscribed astrocytic tumors.
a. 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) that has recurred or progressed on or after treatment with at least 1 line of standard of care therapy.
b. 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. For Cohort C, all gliomas and glioneuronal and neuronal tumors with a known or likely FGFR 1-3 activating mutation are also eligible.
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 FGFR1-3 gene mutation or fusion/rearrangement from tissue.
a. 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) 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.
b. Cohort B: Participants with other 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, 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.
c. 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.
8. MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit. An interva
1. Prior receipt of a selective 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of pemigatinib in participants with recurrent GBM or other primary CNS tumors with an activating FGFR1-3 mutation or fusion/rearrangement.;Secondary Objective: To determine the safety and tolerability of pemigatinib in participants with recurrent GBM or other primary CNS tumors with an activating FGFR1-3 mutation and/or fusion/rearrangement.;Primary end point(s): • ORR in Cohort A, defined as the proportion of participants in Cohort A who achieve a BOR of CR or PR based on RANO as determined by an ICR.<br>• ORR in Cohort B, defined as the proportion of participants in Cohort B who achieve a BOR of CR or PR based on RANO as determined by an ICR.<br>;Timepoint(s) of evaluation of this end point: The schedule for assessments will be performed according to the schedule of activities reported in the protocol.<br>Adverse events will be monitored from the time the participant signs the ICF until at least 30 days after the last dose of study treatment.
- Secondary Outcome Measures
Name Time Method