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)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 83
- 试验地点
- 78
- 主要终点
- Objective Response Rate (ORR) in Participants With Recurrent Glioblastoma Based on Independent Central Review
研究概览
简要总结
This is an open-label, monotherapy study of pemigatinib in participants with recurrent glioblastoma (GBM) or other recurrent gliomas, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors with an activating FGFR1-3 mutation or fusion/rearrangement. This study consists of 2 cohorts, Cohorts A, and B, and will enroll approximately 82 participants into each cohort. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological, cytological, or molecular confirmation of recurrent GBM or other glioma, circumscribed astrocytic glioma, or glioneuronalor neuronal tumors that has recurred.
- •Radiographically measurable disease.
- •. -Karnofsky performance status ≥
- •Life expectancy ≥ 12 weeks.
- •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.
- •MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit.
- •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.
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •Prior receipt of an FGFR inhibitor.
- •Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of study drug.
- •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
- •Candidate for potentially curative surgery.
- •Dexamethasone (or equivalent) > 4 mg daily at the time of study registration
- •Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
- •Diffuse leptomeningeal disease.
- •Radiation therapy administered within 12 weeks before enrollment/first dose of study drug.
- •Known additional malignancy that is progressing or requires active systemic treatment.
研究组 & 干预措施
Cohort A: IDH-wild-type GBM
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 that are recurrent, harboring FGFR1-3 fusions/or other rearrangements, or with a defined FGFR1-3 mutation or in-frame deletion.
干预措施: Pemigatinib (Drug)
Cohort B: Other gliomas other than GBM
Participants with other histopathologically proven gliomas other than GBM, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors that are recurrent, harboring FGFR1-3 fusions/or other rearrangements or with a defined FGFR1-3 activating mutation or in-frame deletion
干预措施: Pemigatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) in Participants With Recurrent Glioblastoma Based on Independent Central Review
时间窗: up to 651 days
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an independent centralized radiological review committee. CR requires all of the following: disappearance of all enhancing measurable/nonmeasurable disease sustained for ≥4 weeks; no new lesions; stable/improved nonenhancing lesions; off corticosteroids/on physiologic replacement doses only and stable/improved clinically. PR requires all of the following: ≥50% decrease, compared with baseline, in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for ≥4 weeks; no progression of nonmeasurable disease; no new lesions; stable or improved nonenhancing lesions on same/lower dose of corticosteroids compared with baseline scan; on a corticosteroid dose not greater than the dose at time of baseline scan and stable/improved clinically.
次要结局
- ORR in Participants With Recurrent Non-glioblastoma Central Nervous System Tumors Based on Independent Central Review(up to 784 days)
- Duration of Confirmed Response Based on Independent Central Review(up to 784 days)
- Duration of Unconfirmed Response Based on Independent Central Review(up to 784 days)
- ORR as Determined by Investigator Assessment(up to 784 days)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)(up to 814 days)
- Number of Participants With Any ≥Grade 3 TEAE(up to 814 days)
- Number of Participants With TEAEs Leading to Discontinuation of Pemigatinib, Pemigatinib Dose Interruption, and Pemigatinib Dose Reduction(up to 814 days)
- Disease Control Rate (DCR) Based on Independent Central Review(up to 784 days)
- Progression-free Survival (PFS) Based on Independent Central Review(up to 784 days)
- Overall Survival(up to 784 days)