Clinical Trials Register

Summary
EudraCT Number:	2021-004740-24
Sponsor's Protocol Code Number:	INCB54828-209
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-02-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-004740-24

A.3

Full title of the trial

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)

Estudio abierto de fase II, multicéntrico, de un solo brazo para evaluar la eficacia y la seguridad de pemigatinib en sujetos con glioblastoma u otros tumores primarios del sistema nervioso central tratados previamente que presentan alteraciones activadoras de FGFR1-3 (FIGHT-209)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

INCB54828-209

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Incyte Corporation
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Incyte Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Incyte Corporation
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	1801 Augustine Cut-Off
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19803
B.5.3.4	Country	United States
B.5.4	Telephone number	+34911594080
B.5.5	Fax number	+13024252734
B.5.6	E-mail	globalmedinfo@incyte.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Pemazyre
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Biosciences Distribution B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pemigatinib
D.3.2	Product code	INCB054828
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMIGATINIB
D.3.9.1	CAS number	1513857-77-6
D.3.9.2	Current sponsor code	INCB054828
D.3.9.3	Other descriptive name	INCB054828
D.3.9.4	EV Substance Code	SUB194579
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Pemazyre
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Biosciences Distribution B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pemigatinib
D.3.2	Product code	INCB054828
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMIGATINIB
D.3.9.1	CAS number	1513857-77-6
D.3.9.2	Current sponsor code	INCB054828
D.3.9.3	Other descriptive name	INCB054828
D.3.9.4	EV Substance Code	SUB194579
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	9.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Pemazyre
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Biosciences Distribution B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pemigatinib
D.3.2	Product code	INCB054828
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMIGATINIB
D.3.9.1	CAS number	1513857-77-6
D.3.9.2	Current sponsor code	INCB054828
D.3.9.3	Other descriptive name	INCB054828
D.3.9.4	EV Substance Code	SUB194579
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	13.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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 therapy

Participantes de ambos sexos, de 18 años, como mínimo, con GBM recurrente u otros tumores recurrentes primarios del SNC con reordenamientos o fusiones de FGFR1-3 que hayan empeorado y que reciban, al menos, uno de los tratamientos de referencia, como quimioterapia y/o radioterapia.

E.1.1.1

Medical condition in easily understood language

Participants with brain tumors harboring FGFR1-3 mutation, who have progressed after at least one standard of care therapy

Participantes con tumores cerebrales que albergan la mutación FGFR1-3, que han progresado después de al menos un tratamiento estándar

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10065147
E.1.2	Term	Malignant solid tumor
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

Determinar la eficacia del pemigatinib en participantes con GBM recurrente u otros tumores primarios recurrentes del SNC con una mutación activadora de FGFR1-3 o un reordenamiento o fusión.

E.2.2

Secondary objectives of the trial

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.

Determinar la seguridad y la tolerabilidad del pemigatinib en participantes con GBM recurrente u otros tumores primarios recurrentes del SNC con una mutación activadora de FGFR1-3 y/o un reordenamiento o fusión.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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 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.
9. 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.
10. Willingness to avoid pregnancy or fathering children based on the criteria below.
a. Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 90 days after the last dose of study drug and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed.
b. Female participants who are WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy from screening through 30 days after the last dose of study pemigatinib and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed.
c. A female participant not considered to be of childbearing potential is eligible.

1. Capacidad para comprender y voluntad de firmar un DCI por escrito para el estudio. 2. Participantes de ambos sexos de 18 años, como mínimo, en el momento de la firma del DCI. 3. Confirmación histológica, citológica o molecular de GBM recurrente u otro tipo de glioma difuso en adultos o de tumores astrocíticos delimitados. a. Para las cohortes A y C: Confirmación histopatológica previa de grado 4 según la OMS de GBM sin mutaciones de IDH o bien diagnóstico molecular de glioma astrocítico difuso sin mutaciones de IDH con características moleculares de GBM de grado 4 según la OMS (el glioma astrocítico requiere la presencia o la amplificación de EGFR, ganancia completa del cromosoma 7 o pérdida completa del cromosoma 10, o mutación del promotor de TERT) con recidiva o empeoramiento durante o después del tratamiento, con al menos uno de los tratamientos de referencia. b. Para las cohortes B y C: Confirmación histopatológica previa, según los criterios de la OMS, de gliomas difusos de tipo adulto que no sean GBM, incluidos el astrocitoma con mutaciones de IDH y el oligodendroglioma con mutaciones de IDH y coeliminación de 1p/19q, así como de tumores astrocíticos delimitados, incluido el astrocitoma pilocítico, con recidiva o empeoramiento durante o después del tratamiento, con al menos uno de los tratamientos de referencia. También serán aptos para la cohorte C todos los gliomas y los tumores glioneuronales y neuronales con una mutación activadora conocida o probable de FGFR 1-3. 4. Enfermedad medible con radiografía (según los criterios RANO). Se consideran medibles las lesiones tumorales que se encuentren en una zona previamente irradiada o en una zona que reciba otro tratamiento locorregional si se ha demostrado claramente el empeoramiento de la lesión. 5. Estado general de Karnofsky ≥ 60. 6. Esperanza de vida ≥12 semanas. 7. Documentación de una mutación genética de FGFR1-3 o fusión/reordenamiento de tejido. a. Cohorte A: Participantes con confirmación histopatológica previa de grado 4 según la OMS de GBM sin mutaciones de IDH o bien diagnóstico molecular de glioma astrocítico difuso sin mutaciones de IDH con características moleculares de GBM de grado 4 según la OMS (el glioma astrocítico requiere la presencia o la amplificación de EGFR, ganancia completa del cromosoma 7 o pérdida completa del cromosoma 10, o mutación del promotor de TERT) con recidiva, que presenten fusiones o reordenamientos de FGFR1-3 (fusiones dentro del marco de lectura de FGFR1-3, cualquier reordenamiento de FGFR2 o reordenamientos de FGFR1/3 con genes de translocación recíproca conocidos). Solo son aptas las fusiones o los reordenamientos de FGFR con un dominio cinasa inalterado. b. Cohorte B: Participantes con confirmación histopatológica previa, según los criterios de la OMS, de gliomas difusos de tipo adulto que no sean GBM, incluidos el astrocitoma con mutaciones de IDH y el oligodendroglioma con mutaciones de IDH y coeliminación de 1p/19q, así como de tumores astrocíticos delimitados, incluido el astrocitoma pilocítico que presenten recidiva y fusiones o reordenamientos de FGFR1-3 (fusiones dentro del marco de lectura de FGFR1-3, cualquier reordenamiento de FGFR2 o reordenamientos de FGFR1/3 con genes de translocación recíproca conocidos). Solo son aptas las fusiones o los reordenamientos de FGFR con un dominio cinasa inalterado. c. Cohorte C: Participantes con confirmación histopatológica previa de GBM sin mutaciones de IDH de grado 4 según la OMS o con diagnóstico molecular de glioma astrocítico difuso sin mutaciones de IDH con características moleculares de grado 4, según la OMS, con recidiva o confirmación histopatológica, según los criterios de la OMS, gliomas difusos que no sean GBM, incluidos el astrocitoma con mutaciones de IDH y el oligodendroglioma con mutaciones de IDH y coeliminación de 1p/19q, así como de tumores astrocíticos delimitados, incluido el astrocitoma pilocítico, con recidiva y una mutación activadora conocida o probable de FGFR1-3. 8. Empeoramiento objetivo documentado mediante RM tras tratamiento previo y ausencia de tratamiento disponible que pueda proporcionar beneficio clínico. Se requiere un intervalo de al menos 12 semanas después de la radioterapia anterior, a menos que haya confirmación histopatológica de tumor recurrente o una nueva intensificación en la RM fuera de la zona de la radioterapia.
9. Muestra tumoral inicial de archivo inferior a 24 meses desde la fecha de la selección. Debe ser un bloque de biopsia o un mínimo de 15 portaobjetos sin tinción de biopsia o de resección de tumor primario o metástasis.
10. Estar de acuerdo en evitar embarazos o engendrar hijos en función de los criterios que aparecen a continuación. (see protocol)

E.4

Principal exclusion criteria

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.

1. Administración previa de un inhibidor selectivo de FGFR.
2. Recepción de medicamentos antineoplásicos o fármacos en investigación para cualquier indicación o motivo en los 28 días anteriores a la primera dosis del fármaco del estudio. Los participantes deben haberse recuperado (≤grado 1) de los AA de los tratamientos administrados previamente.
3. Los participantes pueden haber recibido tratamiento con un número ilimitado de recidivas anteriores, pero no deben haber recibido antes bevacizumab ni otros inhibidores del VEGF/VEGFR.
4. Tratamiento antineoplásico simultáneo.
5. Candidatos a cirugía potencialmente curativa.
6. Dexametasona (o equivalente) >4 mg al día en el momento de la inscripción en el estudio (se permite una dosis más alta de corticoesteroides para el control de los síntomas durante el estudio).
7. Indicios actuales de trastorno corneal o retiniano clínicamente significativo confirmados mediante exploración oftalmológica.
8. Enfermedad leptomeníngea difusa.
9. Radioterapia administrada en el plazo de las 12 semanas anteriores a la inscripción/primera dosis del fármaco del estudio. Se requiere un intervalo de al menos 12 semanas después de la radioterapia anterior, a menos que haya confirmación histopatológica de tumor recurrente o una nueva intensificación en la RM fuera de la zona de la radioterapia.
10. Neoplasia maligna conocida, que empeora o requiere tratamiento sistémico activo. Son excepciones el carcinoma basocelular de la piel, el carcinoma espinocelular en la piel o el cáncer cervicouterino in situ que se haya sometido a tratamiento potencialmente curativo.

E.5 End points

E.5.1

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.
• 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.

• TRO en la cohorte A, definida como la proporción de participantes en la cohorte A que logran una MRG de RC o RP según los criterios RANO, según lo determinado mediante una revisión central independiente.
• TRO en la cohorte B, que se define como la proporción de participantes en la cohorte B que logran una MRG de RC o RP según los criterios RANO, según lo determinado mediante una revisión central independiente.

E.5.1.1

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.
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.

El cronograma de evaluaciones se realizará de acuerdo con el calendario de actividades del protocolo.
Se vigilarán los acontecimientos adversos desde el momento en que el participante firme el DCI hasta, como mínimo, 30 días después de la última dosis del tratamiento del estudio.

E.5.2

Secondary end point(s)

• ORR in Cohorts A and B combined, 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.
• ORR in Cohorts A, B, and C combined, defined as the proportion of participants in Cohorts A, B, and C who achieve a BOR of CR or PR based on RANO as determined by an ICR.
• ORR in Cohort C, 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.
• ORR in each cohort as determined by investigator assessment.
• DCR in Cohorts A and B, respectively, described as the proportion of participants who achieve a CR, PR, or SD as assessed by an ICR.
• PFS in Cohorts A and B, respectively, defined as the time from first dose until progressive disease (according to RANO and assessed by an ICR) or death (whichever occurs first).
• DOR in Cohorts A and B, respectively, 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).
• OS in Cohorts A and B, respectively, defined as the time from first dose of study drug to death of any cause.
• Safety and tolerability in each cohort, assessed by monitoring the frequency and severity of AEs by performing physical examinations, evaluating changes in vital signs and ECGs, and evaluating clinical laboratory blood samples according to NCI CTCAE v5.0.
• Impact on study treatment, assessed by monitoring the frequency of treatment interruptions, dose reductions, and withdrawal of study treatment due to AEs.

• TRO en las cohortes A y B combinadas, definida como la proporción de participantes en las cohortes A y B que logran una MRG de RC o RP según los criterios RANO, según lo determinado mediante una revisión central independiente.
• TRO en las cohortes A, B y C combinadas definida como la proporción de participantes en las cohortes A, B y C que logran una MRG de RC o RP según los criterios RANO, según lo determinado mediante una revisión central independiente.
• TRO en la cohorte C, definida como la proporción de participantes en la cohorte C que logran una MRG de RC o RP según los criterios RANO, según lo determinado mediante una revisión central independiente.
• TRO en cada cohorte según lo determinado por la evaluación del investigador.
• TCE en las cohortes A y B, respectivamente, definida como la proporción de participantes que logran una RC, RP o EE según la evaluación mediante una revisión central independiente.
• SSP en las cohortes A y B, respectivamente, definida como el tiempo desde la primera dosis hasta la progresión de la enfermedad (según los criterios RANO y evaluada mediante una revisión central independiente) o muerte (lo que ocurra primero).
• DR en las cohortes A y B, respectivamente, definida como el tiempo desde la fecha de la primera evaluación de RC o RP hasta la fecha de la primera progresión de la enfermedad (según la RANO y evaluada mediante una revisión central independiente) o muerte
• (lo que ocurra primero).
• SG en las cohortes A y B, respectivamente, definida como el tiempo desde la primera dosis del fármaco del estudio hasta la muerte por cualquier causa.
• Seguridad y tolerabilidad en cada cohorte, evaluadas a partir de la supervisión de la frecuencia y la intensidad de los AA mediante exploraciones físicas, la evaluación de los cambios en las constantes vitales y los ECG y la evaluación de las muestras de sangre para analíticas clínicas de acuerdo con los CTCAE del NCI v5.0.
• Efectos en el tratamiento del estudio, evaluados mediante la supervisión de la frecuencia de las interrupciones del tratamiento, las reducciones de la dosis y la retirada del tratamiento del estudio debido a los AA.

E.5.2.1

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

El calendario de evaluaciones se realizará de acuerdo con el calendario de actividades indicado en el protocolo

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Denmark

France

Germany

Italy

Japan

Netherlands

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

132

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

189

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Upon completion of this study, for participants who are continuing to receive study drug and benefiting from treatment with pemigatinib, the rollover study, INCB 54828-801, is available.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-04-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-22

P. End of Trial
P.	End of Trial Status	Ongoing

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