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

JRCT ID: jRCT2031220352

Registered date:28/09/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Glioblastoma, Adult-type Diffuse Gliomas
• Date of first enrollment: 15/10/2022
• Target sample size: 164
• Countries of recruitment: U.S,A,Japan,Denmark,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Spain,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Cohort A: IDH-wild-type GBM
Pemigatinib13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.

Cohort B: other gliomas other than GBM
Pemigatinib 13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.

Outcome(s)

• Primary Outcome: Cohort A: Overall Response Rate (ORR)

Secondary Outcome

1. Cohort B: ORR
2. Cohorts A and B combined: ORR
3. Cohorts A and B: Disease Control Rate (DCR)
4. Cohorts A and B: Progression-Free Survival (PFS)
5. Cohorts A and B: Overall Survival (OS)
6. Safety and tolerability
7. Cohorts A and B: Duration of Response (DOR)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 99age old
• Gender: Both

Include criteria

1. Histological, cytological, or molecular confirmation of recurrent GBM or other glioma, circumscribed astrocytic glioma, or glioneuronal or neuronal tumors that has recurred.
2. Radiographically measurable disease.
3. Karnofsky performance status >= 60.
4. Life expectancy >= 12 weeks.
5. 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.
6. MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit.
7. 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.
8. Willingness to avoid pregnancy or fathering children.

Exclude criteria

1. Prior receipt of 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.
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 (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).
4. Concurrent anticancer therapy.
5. Candidate for potentially curative surgery.
6. Dexamethasone (or equivalent) > 4 mg daily at the time of study registration.
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.
10. Known additional malignancy that is progressing or requires active systemic treatment.

Related Information

• Primary Sponsor: Ueda Eiji
• Secondary ID(s): NCT05267106