E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors with FGFR2b Overexpression |
Estudio tipo cesta de fase 1b/2, multicéntrico y abierto que evalúa la seguridad y eficacia de bemarituzumab en monoterapia en tumores sólidos con sobreexpresión de FGFR2b (FORTITUDE-301) |
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E.1.1.1 | Medical condition in easily understood language |
A Study Evaluating Bemarituzumab in Solid Tumors with FGFR2b Overexpression |
Estudio que evalúa bemarituzumab en tumores sólidos con sobreexpresión de FGFR2b |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055476 |
E.1.2 | Term | Esophageal squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073364 |
E.1.2 | Term | Ductal adenocarcinoma of pancreas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073077 |
E.1.2 | Term | Intrahepatic cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10033131 |
E.1.2 | Term | Ovarian carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014720 |
E.1.2 | Term | Endometrial adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10008239 |
E.1.2 | Term | Cervical carcinoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase 1b: •To observe the safety and tolerability of bemarituzumab Phase 2: •To evaluate preliminary antitumor activity |
Fase 1b: •Observar la seguridad y la tolerabilidad de bemarituzumab. Fase 2: •Evaluar la actividad antitumoral preliminar. |
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E.2.2 | Secondary objectives of the trial |
Phase 1b: •To evaluate other measures of preliminary antitumor activity •Characterize the PK of bemarituzumab monotherapy Phase 2: •To evaluate other measures of preliminary antitumor activity •To evaluate the safety and tolerability of bemarituzumab •Characterize the PK of bemarituzumab monotherapy |
Fase 1b: •Evaluar otras medidas de la actividad antitumoral preliminar. •Describir la farmacocinética (FC) de bemarituzumab en monoterapia. Fase 2: •Evaluar otras medidas de la actividad antitumoral preliminar. •Evaluar la seguridad y tolerabilidad de bemarituzumab. •Describir la farmacocinética (FC) de bemarituzumab en monoterapia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults with histologically or cytologically confirmed cancer of one of the following types, refractory to or relapsed after at least 1 prior standard therapeutic regimen in the advanced/metastatic setting: - head and neck squamous cell carcinoma: more than or equal to 1 line of therapy -esophageal squamous cell carcinoma: more than or equal to 1 line of therapy -triple-negative breast cancer: more than or equal to 2 lines of therapy -pancreatic ductal adenocarcinoma: more than or equal to 1 line of therapy -Intrahepatic cholangiocarcinoma more than or equal to 1 line of therapy -colorectal adenocarcinoma: more than or equal to 2 lines of therapy -platinum-resistant ovarian epithelial carcinoma, defined as progression during or within 6 months of a platinum containing regimen: more than or equal to 1 line of therapy -endometrial adenocarcinoma: more than or equal to 1 line of therapy -cervical carcinoma: more than or equal to 1 line of therapy -other solid tumors: more than or equal to 1 line of therapy •Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing •Measurable disease per RECIST v1.1 •Adequate hematologic and organ function, defined as follows: -Absolute neutrophil count more than or equal to 1.5 x 109/L -Platelet count more than or equal to 100 x 109/L -Hemoglobin more than or equal to 9 g/dL -AST and ALT less than 3 x upper limit of Normal [ULN] (or < 5 x ULN in case of liver involvement). Total bilirubin less than 1.5 x ULN (or less than 2 x ULN in case of liver involvement OR Gilbert’s disease)
For more details please see section 5.1 Inclusion Criteria within the Protocol |
•Adultos con cáncer confirmado histológica o citológicamente de uno de los siguientes tipos, refractario o en recaída tras al menos 1 régimen terapéutico estándar previo en el entorno avanzado o metastásico: -Carcinoma de células escamosas de cabeza y cuello: ≥ 1 línea de tratamiento. -Carcinoma de células escamosas del esófago: ≥ 1 línea de tratamiento. -Cáncer de mama triple negativo: ≥ 2 líneas de tratamiento. -Adenocarcinoma ductal pancreático: ≥ 1 línea de tratamiento. -Colangiocarcinoma intrahepático: ≥ 1 línea de tratamiento. -Adenocarcinoma colorrectal: ≥ 2 líneas de tratamiento. -Carcinoma epitelial de ovario resistente a platino, definido como la aparición de progresión durante o en los 6 meses siguientes a un régimen con platino: ≥ 1 línea de tratamiento. -Adenocarcinoma de endometrio: ≥ 1 línea de tratamiento. -Carcinoma cervical: ≥ 1 línea de tratamiento. -Otros tumores sólidos: ≥ 1 línea de tratamiento. •El tumor presenta sobreexpresión de FGFR2b, determinada mediante pruebas inmunohistoquímicas (IHQ) realizadas centralmente. •Enfermedad medible según los criterios RECIST v. 1.1. •Función hematológica y orgánica adecuada, definida de la manera siguiente: -Recuento absoluto de neutrófilos ≥ 1,5 x 109/l. -Recuento plaquetario ≥ 100 x 109/l. -Hemoglobina ≥ 9 g/dl. -AST y ALT < 3 x límite superior de la normalidad (LSN) (o < 5 x LSN en caso de afectación hepática). Bilirrubina total < 1,5 x LSN (o < 2 x LSN en caso de afectación hepática O enfermedad de Gilbert).
Para más detalles porfavor ver sección 5.1 Criterios de Inclusión en el Protocolo. |
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E.4 | Principal exclusion criteria |
•Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease •Other solid tumor cohort excludes primary tumors of the CNS, squamous non small cell lung carcinoma, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma •History of other malignancy within the past 2 years (see exceptions within the Protocol) •Impaired cardiac function or clinically significant cardiac disease •Active infection requiring systemic treatment or any uncontrolled infection within 14 days prior to first dose of study treatment •Known human immunodeficiency virus (HIV) infection •History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids •Prior treatment with any investigational selective inhibitor of the FGF-FGFR pathway (unless approved standard of care for tumor indication) •Any anticancer therapy or immunotherapy within 4 weeks prior to enrollment (see additional details within the Protocol) •Major surgical procedure within 28 days prior to first dose of study treatment. •Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.
For more details please see section 5.2 Exclusion Criteria within the Protocol |
•Metástasis en el sistema nervioso central (SNC) no tratadas o sintomáticas o enfermedad leptomeníngea. •La cohorte de otros tumores sólidos excluye los tumores primarios del SNC, el carcinoma de pulmón no microcítico escamoso, el adenocarcinoma gástrico y el adenocarcinoma de la unión gastroesofágica •Antecedentes de otras neoplasias malignas en los últimos 2 años (ver excepciones en el Protocolo) •Deterioro de la función cardíaca o cardiopatía clínicamente significativa •Infección activa que requiera tratamiento sistémico o cualquier infección no controlada en los 14 días antes de la primera dosis del tratamiento del estudio. •Infección conocida por el virus de la inmunodeficiencia humana (VIH) •Antecedentes de enfermedad sistémica o trastornos oftalmológicos que requieran el uso crónico de esteroides oftálmicos •Tratamiento previo con cualquier inhibidor selectivo de la vía del FGF-FGFR en fase de investigación (a menos que esté aprobado como tratamiento estándar para la indicación del tumor). •Cualquier tratamiento anticanceroso o inmunoterapia en las 4 semanas previas a la inclusión (ver detalles adicionales en el Protocolo). •Procedimiento quirúrgico mayor en los 28 días previos a la primera dosis del tratamiento del estudio. •Mujeres en edad fértil con una prueba de embarazo positiva, evaluada en la selección mediante una prueba de embarazo en suero con un alto grado de sensibilidad.
Para más detalles porfavor ver sección 5.2 Criterios de Exclusión en el Protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: •Dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, and clinical laboratory tests Phase 2: •Objective Response (OR) |
Fase 1b: •Toxicidades limitantes de la dosis (TLD), acontecimientos adversos aparecidos durante el tratamiento, acontecimientos adversos relacionados con el tratamiento y cambios clínicamente significativos en las constantes vitales, la agudeza visual y las pruebas analíticas clínicas. Fase 2 •Respuesta objetiva (RO) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoints to be assessed throughout the course of the study. (See Table 1-1 in section 1.3 Schedule of Activities in Protocol) |
Las variables se evaluarán a lo largo del curso del estudio. (Ver tabla 1-1 en la sección 1.3 Calendario de Actividades en el Protocolo) |
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E.5.2 | Secondary end point(s) |
Phase 1 and Phase 2: Objective response (OR) •Disease control (DC) (CR, PR, or stable disease [SD]) •Duration of response (DOR) •Time to response (TTR) •Progression-free survival (PFS) •Overall survival (OS) •PK parameters for bemarituzumab including, but not limited to, AUC, Cmax, and Ctrough •PK parameters for bemarituzumab including, but not limited to, area under the concentration time curve (AUC), maximum observed concentration (Cmax), and the observed concentration at the end of a dose interval (Ctrough) |
Fase 1 y fase 2: •Respuesta objetiva (RO) •Control de la enfermedad (CE)(RC, RP o enfermedad estable [EE]). •Duración de la respuesta (DR) •Tiempo hasta la respuesta (THR) •Supervivencia libre de progresión (SLP) •Supervivencia global (SG) •Parámetros FC de bemarituzumab que incluyen, entre otros, el área bajo la curva (AUC), la concentración sérica máxima observada (Cmáx.) y la concentración observada al final de un intervalo de dosis (Ctrough). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OR, DC, DOR, TTR, PFS: •Radiographic assessment to be performed every 8 weeks (± 7 days) until week 56 and then every 12 weeks (± 14 days) until radiographic progression or initiation of subsequent anticancer therapy. OS: •To be assessed after subject enrollment and throughout the course of the study. After safety follow-up subjects will undergo long term follow-up for survival approximately every 3 months (± 1 month) for up to 2 years from the first dose of bemarituzumab. (See Table 1-1 in section 1.3 Schedule of Activities in Protocol) |
RO, CE, DR, THR, SLP: •Evaluación radiográfica cada 8 semanas (± 7 días) hasta la semana 56 y luego cada 12 semanas (± 14 días) hasta la progresión radiográfica o iniciación de la subsecuente terapia anticancerosa. SG: •Evaluación tras la inclusión del sujeto y durante el curso del estudio. Tras el seguimiento de seguridad los pacientes tendrán un seguimiento a largo plazo de supervivencia cada 3 meses (± 1 mes) hasta 2 años tras la primera dosis de bemarituzumab. (Ver tabla 1-1 en la sección 1.3 Calendario de Actividades en el Protocolo). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Assess tolerability, characterize immunogenicity and biomarkers |
Evaluar la tolerabilidad, caracterizar la inmunogenicidad y los biomarcadores |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | No |
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 |
Argentina |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Turkey |
United States |
Austria |
Belgium |
Czechia |
Denmark |
Finland |
France |
Greece |
Hungary |
Italy |
Poland |
Portugal |
United Kingdom |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, long-term follow-up, antibody testing), as applicable. |
La fecha de fin del estudio se define como la fecha en que el último sujeto de todos los centros es evaluado o recibe una intervención para la evaluación en el estudio (p.e, la última visita del último sujeto), incluyendo cualquier parte adicional del estudio (p.e, seguimiento a largo plazo, test de anticuerpos), según aplique. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |