E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Solid Tumors with FGFR2b Overexpression |
Tumori solidi con sovraespressione di FGFR2b |
|
E.1.1.1 | Medical condition in easily understood language |
Solid Tumors with Fibroblast growth factor receptor 2b (FGFR2b) Overexpression |
Tumori solidi con sovraespressione del recettore del fattore di crescita dei fibroblasti 2b (FGFR2b) |
|
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 | 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 | 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) |
|
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) |
|
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) |
|
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) |
|
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) |
|
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) |
|
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) |
|
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) |
|
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: • Osservare la sicurezza e la tollerabilità di bemarituzumab
Fase 2: • Valutare l’attività antitumorale preliminare |
|
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: - Valutare altre misure di attività antitumorale preliminare - Caratterizzare la PK di bemarituzumab in monoterapia
Fase 2: - Valutare altre misure dell'attività antitumorale preliminare - Valutare la sicurezza e la tollerabilità di bemarituzumab - Caratterizzare la PK di bemarituzumab in monoterapia |
|
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 |
- Adulti con cancro confermato istologicamente o citologicamente di uno dei seguenti tipi, refrattario o recidivato dopo almeno 1 precedente regime terapeutico standard in stadio avanzato/metastatico: - carcinoma squamoso della testa e del collo: più di 1 o 1 linea di terapia -carcinoma a cellule squamose dell'esofago: più di 1 o 1 linea di terapia -carcinoma mammario triplo negativo: più di 2 o 2 linee di terapia -adenocarcinoma duttale pancreatico: più di 1 o 1 linea di terapia -colangiocarcinoma intraepatico: più di 1 o 1 linea di terapia adenocarcinoma del colon-retto: più di 2 o 2 linee di terapia -carcinoma epiteliale ovarico resistente al platino, definito come progressione durante o entro 6 mesi da un regime contenente platino: più di 1 o 1 linea di terapia -adenocarcinoma endometriale: più di 1 linea di terapia o 1 -carcinoma cervicale: più di 1 o 1 linea di terapia -altri tumori solidi: più di 1 o 1 linea di terapia -Il tumore sovraesprime FGFR2b come determinato dal test di immunoistochimica (IHC) eseguito a livello centrale -Malattia misurabile secondo RECIST v1.1 -Funzione ematologica e d'organo adeguata, definita come segue: -Conta dei neutrofili assoluta superiore o uguale a 1,5 x 109/L -Conta delle piastrine maggiore o uguale a 100 x 109/L -Emoglobina maggiore o uguale a 9 g/dl -AST e ALT inferiori a 3 x limite superiore di normalità [ULN] (o < 5 x ULN in caso di coinvolgimento del fegato). Bilirubina totale inferiore a 1,5 x ULN (o inferiore a 2 x ULN in caso di interessamento epatico o malattia di Gilbert)
Per maggiori dettagli si prega di consultare la sezione 5.1 Criteri di inclusione all'interno del protocollo |
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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 FGFFGFR 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 |
-Metastasi del sistema nervoso centrale (SNC) non trattate o sintomatiche o malattia leptomeningea -La coorte di altri tumori solidi esclude i tumori primari del SNC, il carcinoma polmonare squamoso non a piccole cellule, l'adenocarcinoma gastrico e l'adenocarcinoma della giunzione gastroesofagea -Storia di altre neoplasie negli ultimi 2 anni (vedi eccezioni nel protocollo) -Funzione cardiaca compromessa o malattia cardiaca clinicamente significativa -Infezione attiva che richiede un trattamento sistemico o qualsiasi infezione non controllata nei 14 giorni precedenti la prima dose del trattamento dello studio -Infezione nota da virus dell'immunodeficienza umana (HIV) -Storia di malattie sistemiche o disturbi oftalmologici che richiedono l'uso cronico di steroidi oftalmici -Trattamento precedente con qualsiasi inibitore selettivo sperimentale del percorso FGFFGFR (a meno che non sia stato approvato lo standard di cura per l'indicazione del tumore) -Qualsiasi terapia antitumorale o immunoterapia nelle 4 settimane precedenti l'arruolamento (vedi dettagli aggiuntivi nel protocollo) -Procedura chirurgica importante entro 28 giorni prima della prima dose di trattamento dello studio. -Soggetti femminili in età fertile con un test di gravidanza positivo valutato allo screening con un test di gravidanza su siero altamente sensibile.
Per maggiori dettagli si prega di consultare la sezione 5.2 Criteri di esclusione all'interno del protocollo |
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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 1: -Tossicità limitanti la dose (DLTs), eventi avversi legati al trattamento, eventi avversi legati al trattamento e cambiamenti clinicamente significativi dei segni vitali, dell'acuità visiva e dei test clinici di laboratorio Fase 2: -Risposta obiettiva (OR) |
|
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) |
Endpoint da valutare nel corso dello studio. (Vedi Tabella 1-1 nella sezione 1.3 Programma delle attività del protocollo) |
|
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 e Fase 2: Risposta obiettiva (OR) -Controllo della malattia (DC) (CR, PR, o malattia stabile [SD]) -Durata della risposta (DOR) -Tempo alla risposta (TTR) -Sopravvivenza libera da progressione (PFS) -Sopravvivenza complessiva (OS) -Parametri PK per bemarituzumab inclusi, ma non limitati a, AUC, Cmax e Ctrough Parametri PK per bemarituzumab compresi, ma non limitati a, area sotto la curva concentrazione-tempo (AUC), concentrazione massima osservata (Cmax), e la concentrazione osservata alla fine di un intervallo di dosaggio (Ctrough)) |
|
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 followup 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) |
OR, DC, DOR, TTR, PFS: -Valutazione radiografica da eseguire ogni 8 settimane (± 7 giorni) fino alla settimana 56 e poi ogni 12 settimane (± 14 giorni) fino alla progressione radiografica o all'inizio della successiva terapia antitumorale. OS: -Da valutare dopo l'arruolamento dei soggetti e per tutto il corso dello studio. Dopo il follow-up di sicurezza i soggetti saranno sottoposti a un follow-up a lungo termine per la sopravvivenza approssimativamente ogni 3 mesi (± 1 mese) per un massimo di 2 anni dalla prima dose di bemarituzumab. (Vedere la Tabella 1-1 nella sezione 1.3 Schema delle attività del protocollo) |
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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 |
Valutare la tollerabilità, caratterizzare l'immunogenicità e i biomarcatori |
|
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 |
Phase 1b/2 study |
Studio di Fase1b/2 |
|
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 6 |
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 | Information not present in EudraCT |
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, Democratic People's Republic of |
Mexico |
Russian Federation |
Turkey |
United States |
Austria |
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
|
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 data di fine dello studio è definita come la data in cui l'ultimo soggetto in tutti i centri è valutato o riceve un intervento per la valutazione dello studio (cioè, l'ultima visita del soggetto), compresa qualsiasi parte aggiuntiva dello studio (es. follow-up a lungo termine, test degli anticorpi), come meglio applicabile. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |