| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/Refractory Follicular Lymphoma |
| Linfoma follicolare recidivato o refrattario |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed/Refractory Follicular Lymphoma |
| Linfoma follicolare recidivato o refrattario |
|
| 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 | 24.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10085128 |
| E.1.2 | Term | Follicular lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| The purpose of this randomized Phase 3 study is to evaluate the efficacy, safety, and tolerability of epcoritamab 48 mg in combination with R2 compared to R2 alone in subjects with R/R FL. |
| Lo scopo di questo studio randomizzato di Fase 3 è quello di valutare efficacia, sicurezza e tollerabilità di epcoritamab 48 mg in combinazione con R2 rispetto a R2 da solo in soggetti affetti da linfoma follicolare R/R. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows:
• To evaluate whether epcoritamab 48 mg in combination with R2 compared to R2 alone can improve clinical outcomes as measured by key secondary endpoints (including CR, best overall response [BOR], overall survival [OS], and minimal residual disease [MRD] negativity) in subjects with R/R FL.
• To evaluate whether epcoritamab 24 mg in combination with R2 compared to R2 alone can improve PFS in subjects with relapsed/refractory (R/R) FL.
• To evaluate whether epcoritamab 24 mg in combination with R2 compared to R2 alone can improve clinical outcomes as measured by key secondary endpoints (including CR, BOR, OS, and MRD negativity) in subjects with R/R FL.
|
• Valutare se epcoritamab 48 mg in combinazione con R2 rispetto a R2 da solo sia in grado di migliorare gli esiti clinici misurati in base agli endpoint secondari chiave (fra cui CR, miglior risposta globale [best overall response, BOR], sopravvivenza globale (OS) e negatività per malattia minima residua (minimal residual disease, MRD) in soggetti con linfoma follicolare R/R.
• Valutare se epcoritamab 24 mg in combinazione con R2 rispetto a R2 da solo sia in grado di migliorare il parametro PFS in soggetti con linfoma follicolare recidivato/refrattario (R/R)
• Valutare se epcoritamab 24 mg in combinazione con R2 rispetto a R2 da solo sia in grado di migliorare gli esiti clinici misurati in base agli endpoint secondari chiave (fra cui CR, BOR, OS e negatività per MRD) in soggetti con linfoma follicolare R/R. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject must be at least 18 years old.
2. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2.
3. Subject has:
• Fluorodeoxyglucose-positron emission tomography (FDG PET) scan demonstrating positive lesion
compatible with computed tomography (CT) or magnetic resonance image (MRI)-defined anatomical
tumor sites AND
• = 1 measurable nodal lesion (long axis = 1.5 cm and short axis > 1.0 cm) or = 1 measurable extra-nodal
lesion (long axis = 1.0 cm) on CT scan or magnetic resonance image (MRI)
4. Subject must have histologically confirmed Grade 1 to 3a FL according to the World Health Organization (WHO) 2016 classification with no evidence of histologic transformation to an aggressive lymphoma at most recent representative tumor biopsy and CD20+ on a representative tumor biopsy based on the pathology report.
5. Subject must have R/R disease to at least one prior systemic regimen that contained an anti-CD20 monoclonal antibody in combination with (an)other anti-lymphoma agent(s). (Subject who received only prior anti-CD20 monoclonal antibody monotherapy is not eligible.)
6. Subject must be eligible to receive R2 per investigator determination
|
1. Il soggetto deve essere di età almeno pari a 18 anni
2. il soggetto deve presentare un punteggio ECOG (Eastern Cooperative Oncology Group) relativo allo stato funzionale compreso fra 0 e 2.
3. Soggetto con:
• Scansione PET con FDG (tomografia a emissione di positroni con fluorodesossiglucosio) con riscontro di lesione positiva compatibile con siti anatomici tumorali identificati mediante tomografia computerizzata (TAC) oppure risonanza magnetica (RM) IN AGGIUNTA A
• = 1 lesione linfonodale misurabile (asse lungo =1,5 cm e asse corto > 1 cm) oppure = 1 lesione exxtranodale misurabile (asse lungo = 1,0 cm) alla scansione TAC o RM
4. Il soggetto deve presentare linfoma follicolare di Grado compreso fra 1 e 3a confermato istologicamente in accordo alla classificazione dell’Organizzazione Mondiale della Sanità (OMS) 2016, senza alcuna evidenza di trasformazione istologica in linfoma aggressivo alla più recente biopsia rappresentativa del tumore, e CD20+ a una biopsia tumorale rappresentativa in base al referto istologico.
5. Il soggetto deve avere malattia R/R ad almeno un regime sistemico pregresso contenente un anticorpo monoclonale anti-CD20 in combinazione con uno o più altri agenti antilinfoma. (Non sono eleggibili i soggetti che abbiano ricevuto solo una monoterapia pregressa con anticorpo monoclonale anti-CD20).
6. Il soggetto deve essere eleggibile a ricevere R2 secondo quanto determinato dal medico sperimentatore |
|
| E.4 | Principal exclusion criteria |
1. Subject must not have documented refractoriness to lenalidomide, with refractoriness defined as:
o Best response to lenalidomide of stable disease or progressive disease, or
o Progressive disease within 6 months of completion of lenalidomide therapy
2. Subjects must not have had lenalidomide exposure within 12 months prior to randomization |
Il soggetto non deve presentare refrattarietà documentata alla lenalidomide, ove per refrattarietà si intende:
o Miglior risposta alla lenalidomide di malattia stabile o malattia progressiva, oppure
o Progressione di malattia entro 6 mesi dalla conclusione della terapia con lenalidomide
2. I soggetti non devono aver avuto esposizione alla lenalidomide nei 12 mesi precedenti la randomizzazione |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS): duration from the date of randomization to the date of disease progression determined by Lugano criteria per Independent Review Committee (IRC), or death, whichever occurs first.
|
| Sopravvivenza libera da progressione (PFS): tempo intercorso fra la data di randomizzazione e la data della progressione di malattia, determinata in base a criteri di Lugano dal comitato IRC (Independent Review Committee) oppure fino al decesso, quale di questi eventi avvenga per primo |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Throughout the study. Survival follow-up will continue until death, withdrawal of the subject, lost to follow up, study discontinuation, or study termination by the Sponsor, whichever comes first |
| Nel corso dell’intero studio. Il follow-up di sicurezza proseguirà fino al decesso, al ritiro del soggetto, a quando il soggetto risulta perso al follow-up, fino all’interruzione della partecipazione allo studio oppure fino all’interruzione dello studio da parte del promotore, quale di questi eventi avvenga per primo |
|
| E.5.2 | Secondary end point(s) |
•Complete Response (CR) during the study, determined by Lugano criteria, as assessed by IRC
•Best overall response (BOR) of CR or partial response (PR), determined by Lugano criteria, as assessed by IRC
•Overall survival (OS)
•Minimal residual disease (MRD) negativity
|
• Risposta Completa (CR) nel corso dello studio, determinata dal comitato IRC sulla base dei criteri di Lugano
• Miglior risposta globale (BOR) rappresentata da CR o da risposta parziale (partial response, PR), determinata dal comitato IRC sulla base dei criteri di Lugano
• Sopravvivenza globale (overall survival, OS)
• Negatività per malattia minima residua (minimal residual disease, MRD) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-CR/BOR: Throughout the study.
-MRD: Throughout study till Post-Treatment Follow-up visits which will occur for a period of 5 years after the last subject has been randomized or until discontinuation, whichever comes first.
-Survival: Throughout the study until death, withdrawal of the subject, lost to follow up, study discontinuation, or study termination by the Sponsor, whichever comes first |
- CR/BOR: Per l’intera durata dello studio.
- MRD: Per l’intera durata dello studio fino alle visite di Follow-up Post-trattamento che avranno luogo per un periodo di 5 anni dopo la randomizzazione oppure l’interruzione della partecipazione dell’ultimo soggetto, quale di questi eventi avvenga per primo
- Sopravvivenza: Per l’intera durata dello studio fino al decesso, fino al ritiro del soggetto, fino a quando il soggetto risulta perso al follow-up, fino all’interruzione della partecipazione allo studio oppure all’interruzione dello studio da parte del Promotore, quale di questi eventi avvenga per primo |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 120 |
| 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 |
| China |
| Israel |
| Japan |
| Korea, Republic of |
| New Zealand |
| Puerto Rico |
| South Africa |
| Taiwan |
| United States |
| Austria |
| France |
| Poland |
| Sweden |
| Netherlands |
| Spain |
| Switzerland |
| Czechia |
| Germany |
| Greece |
| Italy |
| Belgium |
| Denmark |
| Hungary |
| Slovakia |
| Turkey |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 global end of this study shall be defined as the point at which all enrolled subjects have completed all study-specified follow-up (last subject, last visit in the last country where the study was conducted) or the last subject dies or withdraws from the study in the last country where the study was conducted. However, the maximum trial duration is 5 years after last subject has been enrolled. |
| Per fine globale di questo studio clinico si intende la tempistica in cui tutti i soggetti arruolati avranno completato tutto il follow-up specificato dallo studio (ultimo soggetto, ultima visita nell’ultima nazione dove lo studio è stato condotto) oppure decesso dell’ultimo soggetto o ritiro dell’ultimo soggetto dallo studio nell’ultima nazione dove lo studio è stato condotto. Tuttavia, la durata massima della sperimentazione è di 5 anni dopo l’arruolamento dell’ultimo soggetto. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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