FIGHT-209: 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

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05267106
• Collaborator: (none)
• Enrollment: 189
• Locations: 84
• Arms: 3
• Anticipated Duration (Months): 35.5
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 Design

• Study Type: Interventional
• Anticipated 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.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
• Anticipated Primary Completion Date: May 5, 2025
• Anticipated Study Completion Date: May 5, 2025

Arms and Interventions

Arm	Intervention/Treatment
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).	Drug: Pemigatinib; 13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.; Other Names: NCB054828
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).	Drug: Pemigatinib; 13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.; Other Names: NCB054828
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.	Drug: Pemigatinib; 13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.; Other Names: NCB054828

Outcome Measures

Primary Outcome Measures

1. Cohort A: Overall Response Rate (ORR) [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).

2. Cohort B: ORR [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

1. Cohorts A and B combined: ORR [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.

2. Cohorts A, B, and C combined: ORR [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.

3. Cohort C: ORR [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.

4. Cohorts A, B and C: ORR [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

5. Cohorts A and B: Disease Control Rate (DCR) [Up to 3 months]

   described as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR.

6. Cohorts A and B: Progression-Free Survival (PFS) [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).

7. Cohorts A and B: Duration of Response (DOR) [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).

8. Cohorts A and B: Overall Survival (OS) [Up to 3 months]

   defined as the time from first dose of study drug to death of any cause.

9. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Valkyrie Clinical Trials	Beverly Hills	California	United States	90211
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	Providence Medical Foundation	Fullerton	California	United States	92835
4	Usc Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	Stanford Neuroscience Health Center	Sacramento	California	United States	94304
6	Sharp Memorial Hospital	San Diego	California	United States	92123
7	University of California San Francisco	San Francisco	California	United States	94143
8	Providence St Joseph Hospital Orange Center For Cancer Prevention and Treatment	Santa Monica	California	United States	90404
9	Yale Cancer Center	New Haven	Connecticut	United States	06510-3220
10	Lynn Cancer Institute Marcus Neuroscience Institute	Boca Raton	Florida	United States	33486-2304
11	Baptist Md Anderson Cancer Center	Jacksonville	Florida	United States	32207
12	Miami Cancer Institute	Miami	Florida	United States	33176
13	Orlando Health Cancer Institute Downtown Orlando	Orlando	Florida	United States	32806
14	H. Lee Moffitt Cancer Center and Research Institute Hospital	Tampa	Florida	United States	33612-9497
15	Northwestern University	Chicago	Illinois	United States	60611
16	Rush University Medical Center - Consultants in Hematology	Chicago	Illinois	United States	60612
17	University of Iowa Hospital and Clinics	Iowa City	Iowa	United States	52242
18	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
19	University of Minnesota Health Clinics and Surgery Center	Minneapolis	Minnesota	United States	55455
20	Northwell Health	Lake Success	New York	United States	11042
21	Rhodes Center For Glioblastoma At Newyork - Presbyterian Hospital	New York	New York	United States	10033
22	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
23	Vidant Medical Center	Greenville	North Carolina	United States	27834
24	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina	United States	27157
25	UC Health At Cincinnati Va Medical Center	Cincinnati	Ohio	United States	45229
26	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
27	The Ohio State University	Columbus	Ohio	United States	43210
28	University of Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19104
29	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania	United States	15232
30	Tennessee Oncology	Chattanooga	Tennessee	United States	37403
31	Tennessee Oncology	Nashville	Tennessee	United States	37203
32	Baylor Scott and White Research Institute	Dallas	Texas	United States	75246
33	John Peter Smith Hospital	Fort Worth	Texas	United States	76104
34	Houston Methodist Hospital	Houston	Texas	United States	77030
35	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
36	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
37	Aalborg Universitets Hospital	Aalborg		Denmark	09000
38	Aarhus University Hospital	Aarhus		Denmark	08200
39	Rigshospitalet Uni of Hospital of Copenhagen	Copenhagen		Denmark	02100
40	Odense University Hospital	Odense C		Denmark	05000
41	Chru de Lille Hopital Claude Huriez	Lille Cedex		France	59037
42	Chu Hopital de La Timone	Marseille		France	13005
43	Hospital Universitaire Pitie-Salpetriere	Paris		France	75013
44	Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole	Toulouse		France	31059
45	Universitatsklinikum Bonn Aoer	Bonn		Germany	53127
46	Klinikum Der Johann Wolfgang Goethe University	Frankfurt		Germany	60528
47	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
48	University Hospital Tuebingen	Tuebingen		Germany	72076
49	Ospedale Bellaria	Bologna		Italy	40139
50	Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele	Milano		Italy	20132
51	Iov - Istituto Oncologico Veneto Irccs	Padova		Italy	35128
52	Irccs Istituto Clinico Humanitas	Rozzano		Italy	20089
53	Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza	Torino		Italy	10124
54	University of Tokyo Hospital	Bunkyo-ku		Japan	113-8655
55	National Cancer Center Hospital	Chuo-ku		Japan	104-0045
56	Kyushu University Hospital	Fukuoka-shi		Japan	812-8582
57	Kyoto University Hospital	Kyoto-shi		Japan	606-8507
58	Nagoya University Hospital	Nagoya-shi		Japan	466-8560
59	Tohoku University Hospital	Sendai-shi		Japan	980-8574
60	Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands	1066 CX
61	Erasmus Mc Cancer Institute	Rotterdam		Netherlands	3015 GD
62	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX
63	Hospital Del Mar	Barcelona		Spain	08003
64	Hospital General Universitario Vall D Hebron	Barcelona		Spain	08035
65	Hospital Clinic de Barcelona	Barcelona		Spain	08036
66	Hospital de La Santa Creu I Sant Pau	Barcelona		Spain	08041
67	Ico Girona Hospital Universitari de Girona Dr Josep Trueta	Girona		Spain	17007
68	Ico Institut Catala D Oncologia	L'hospitalet de Llobregat		Spain	08908
69	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
70	Hospital Universitario Ramon Y Cajal	Madrid		Spain	28034
71	Fundacion Jimenez Diaz University Hospital	Madrid		Spain	28040
72	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
73	Hospital Universitario Hm Sanchinarro	Madrid		Spain	28050
74	Clinica Universidad de Navarra (Cun)	Pamplona		Spain	31008
75	Hospital General de Catalunya	Sant Cugat Del Valles		Spain	08190
76	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
77	Hospital General Universitario de Valencia	Valencia		Spain	46014
78	Addenbrooke'S Hospital	Cambridge		United Kingdom	CB2 0QQ
79	Velindre Cancer Centre	Cardiff		United Kingdom	CF14 2TL
80	St James'S University Hospital	Leeds		United Kingdom	LS9 7TF
81	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
82	The Royal Marsden Nhs Foundation Trust - Sutton	London		United Kingdom	SW36JJ
83	The Christie Nhs Foundation Trust Uk	Manchester		United Kingdom	M20 4BX
84	The Clatterbridge Cancer Centre	Wirral		United Kingdom	CH63 4JY

Sponsors and Collaborators

• Incyte Corporation

Investigators

• Study Director: Luisa Veronese, MD, Incyte Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT05267106
• Other Study ID Numbers: INCB 54828-209
• First Posted: Mar 4, 2022
• Last Update Posted: Jul 27, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: 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: Glioblastoma; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms

Study Results

No Results Posted as of Jul 27, 2022