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)
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| ClinicalTrials.gov Identifier: NCT05267106 |
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Recruitment Status :
Recruiting
First Posted : March 4, 2022
Last Update Posted : December 2, 2022
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Sponsor:
Incyte Corporation
Information provided by (Responsible Party):
Incyte Corporation
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Adult-type Diffuse Gliomas | Drug: Pemigatinib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 189 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This study consists of 3 cohorts and participants will receive pemigatinib 13.5 mg QD on a 2-week on-therapy and 1-week off-therapy schedule. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | May 20, 2022 |
| Estimated Primary Completion Date : | January 30, 2026 |
| Estimated Study Completion Date : | January 30, 2026 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Pemigatinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A: IDH-wild-type GBM
Participants with recurrent isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM) harboring fibroblast growth factor receptors 1 and/or 3 (FGFR1-3) fusions or rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner).
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Drug: Pemigatinib
13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.
Other Name: NCB054828 |
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Experimental: Cohort B: primary CNS tumors and adult-type diffuse gliomas
Participants with other recurrent primary central nervous system (CNS) tumors, adult-type diffuse gliomas, including IDH-mutant astrocytoma, IDH-mutant and 1p/19q codeleted oligodendroglioma, or pilocytic astrocytomas, harboring FGFR1-3 fusions or rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, FGFR1/3 rearrangement with known partner).
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Drug: Pemigatinib
13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.
Other Name: NCB054828 |
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Experimental: Cohort C: GBM or recurrent primary CNS tumors
Any recurrent GBM or recurrent primary CNS tumor, including adult-type diffuse gliomas and pilocytic astrocytomas, with a known or likely FGFR1-3 activating mutation. All gliomas and glioneuronal and neuronal tumors with a known or likely FGFR 1-3 activating mutation are also eligible.
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Drug: Pemigatinib
13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.
Other Name: NCB054828 |
Primary Outcome Measures :
- Cohort A: Overall Response Rate (ORR) [ Time Frame: Up to 3 months ]Defined as the proportion of participants in Cohort A who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an Independent Central Radiology (ICR).
- Cohort B: ORR [ Time Frame: Up to 3 months ]Defined as the proportion of participants who achieve a CR or PR based on RECIST v1.1. Response will be determined by an ICR review.
Secondary Outcome Measures :
- Cohorts A and B combined: ORR [ Time Frame: Up to 3 months ]defined as the proportion of participants in Cohorts A and B who achieve a BOR of CR or PR based on RANO as determined by an ICR.
- Cohorts A, B, and C combined: ORR [ Time Frame: Up to 3 months ]defined as the proportion of participants in Cohorts A, B, and C combined who achieve a BOR of CR or PR based on RANO as determined by an ICR.
- Cohort C: ORR [ Time Frame: Up to 3 months ]defined as the proportion of participants in Cohort C who achieve a BOR of CR or PR based on RANO as determined by an ICR.
- Cohorts A, B and C: ORR [ Time Frame: Up to 3 months ]proportion of participants in each cohort who achieve a BOR of CR or PR based on RANO as determined by investigator assessment
- Cohorts A and B: Disease Control Rate (DCR) [ Time Frame: Up to 3 months ]described as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR.
- Cohorts A and B: Progression-Free Survival (PFS) [ Time Frame: Up to 3 months ]defined as the time from first dose until progressive disease (according to RANO and assessed by an ICR) or death (whichever occurs first).
- Cohorts A and B: Duration of Response (DOR) [ Time Frame: Up to 3 months ]defined as the time from the date of first assessment of CR or PR until the date of the first progressive disease (according to RANO and assessed by an ICR), or death (whichever is first).
- Cohorts A and B: Overall Survival (OS) [ Time Frame: Up to 3 months ]defined as the time from first dose of study drug to death of any cause.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 3 months ]TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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.
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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 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. 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05267106
Contacts
| Contact: Incyte Corporation Call Center (US) | 1.855.463.3463 | medinfo@incyte.com | |
| Contact: Incyte Corporation Call Center (ex-US) | +800 00027423 | eumedinfo@incyte.com |
Locations
Show 83 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
| Study Director: | Luisa Veronese, MD | Incyte Corporation |
| Responsible Party: | Incyte Corporation |
| ClinicalTrials.gov Identifier: | NCT05267106 |
| Other Study ID Numbers: |
INCB 54828-209 |
| First Posted: | March 4, 2022 Key Record Dates |
| Last Update Posted: | December 2, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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. |
| URL: | https://www.incyte.com/our-company/compliance-and-transparency |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Incyte Corporation:
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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 |
Additional relevant MeSH terms:
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Glioblastoma Glioma Nervous System Neoplasms Central Nervous System Neoplasms Astrocytoma Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases |