E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anti-PD1-refractory/relapsed, unresectable Stage III or IV melanoma |
Melanoma anti-PD1-refrattario/recidivante, di stadio III o IV non resecabile. |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced black skin cancer that is resistant to approved therapies |
Cancro della pelle nero avanzato resistente alle terapie approvate |
|
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 | 10072449 |
E.1.2 | Term | Desmoplastic melanoma |
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 | HLT |
E.1.2 | Classification code | 10027156 |
E.1.2 | Term | Skin melanomas (excl ocular) |
E.1.2 | System Organ Class | 100000004858 |
|
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 | 10024218 |
E.1.2 | Term | Lentigo maligna |
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 | 10024220 |
E.1.2 | Term | Lentigo maligna 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024223 |
E.1.2 | Term | Lentigo maligna stage III |
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 | 10024224 |
E.1.2 | Term | Lentigo maligna stage IV |
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 | 10025650 |
E.1.2 | Term | Malignant melanoma |
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 | 10025670 |
E.1.2 | Term | Malignant melanoma stage III |
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 | 10025671 |
E.1.2 | Term | Malignant melanoma stage IV |
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 | 10066600 |
E.1.2 | Term | Melanoma 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 | PT |
E.1.2 | Classification code | 10027480 |
E.1.2 | Term | Metastatic malignant melanoma |
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 | 10079054 |
E.1.2 | Term | Naevoid melanoma |
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 | 10029488 |
E.1.2 | Term | Nodular melanoma |
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 | 10042551 |
E.1.2 | Term | Superficial spreading melanoma stage III |
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 | 10042552 |
E.1.2 | Term | Superficial spreading melanoma stage IV |
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 | 10042553 |
E.1.2 | Term | Superficial spreading melanoma stage unspecified |
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 |
To demonstrate the anti-tumor activity of BNT111 + cemiplimab (Arm 1) in terms of objective response rate (ORR) according to RECIST 1.1 |
Dimostrare l’attività anti-tumorale di BNT111 + cemiplimab (Braccio 1) in termini di tasso di risposta obiettiva (ORR) secondo RECIST 1.1 |
|
E.2.2 | Secondary objectives of the trial |
•To assess the anti-tumor activity of each single-agent (i.e., BNT111 and cemiplimab, respectively) in terms of ORR according to RECIST 1.1. •To assess additional measures of antitumor activity of BNT111 + cemiplimab, and each single agent according to RECIST 1.1. •To assess overall survival of BNT111 + cemiplimab (Arm 1). •To assess the safety and tolerability profile of BNT111 + cemiplimab, as well as BNT111 and cemiplimab as single agents. •To assess health-related quality of life (HRQoL) of patients treated with BNT111 + cemiplimab and of patients receiving BNT111 and cemiplimab as single agents as measured by the European organization for research and treatment of cancer quality-of-Life questionnaire core 30 items (EORTC QLQ-C30). |
-Valutare l’attività antitumorale di ciascun singolo agente (cioè BNT111 e cemiplimab) in termini di ORR in base a RECIST 1.1 -Valutare le misure aggiuntive di attività antitumorale di BNT111 + cemiplimab, e ciascun agente singolo in base a RECIST 1.1 -Valutare la sopravvivenza globale di BNT111 + cemiplimab (Braccio 1) -Valutare il profilo di sicurezza e tollerabilità di BNT111 + cemiplimab, e di BNT111 e cemiplimab come agenti singoli. -Valutare la qualità della vita correlata alla salute (HRQoL) di pazienti trattati con BNT111 + cemiplimab e di pazienti che ricevono BNT111 e cemiplimab come agenti singoli, misurata secondo i criteri del questionario QLQ-C30 della European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must have histologically confirmed unresectable Stage III or IV (metastatic) cutaneous melanoma and measurable disease by RECIST 1.1. • Patients must have confirmed disease progression on/after approved anti-PD1 regimen for melanoma as defined by RECIST 1.1 • Previous exposure to approved anti-PD1 containing regimen for at least 12 consecutive weeks and • Radiological progression to be confirmed by 2 scans 4-12 weeks apart. If progression is accompanied by new symptoms or deterioration of performance status not attributed to toxicity, one scan is sufficient. • Progression must be while on treatment with approved anti-PD1 regimen for melanoma or within 6 months of discontinuing anti-PD1, and regardless of any intervening therapy. • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =1. • Patients must have serum lactate dehydrogenase (LDH) = ULN.
Please refer to the protocol for a full description of the inclusion criteria. |
• I pazienti devono avere un melanoma cutaneo confermato istologicamente di Stadio III o IV (metastatico) non resecabile e malattia misurabile mediante RECIST 1.1. • I pazienti devono avere progressione della malattia confermata al momento o dopo il regime anti PD1 approvato per il melanoma definito da RECIST 1.1. • Precedente esposizione ad un regime approvato contenente anti-PD1 per almeno 12 settimane consecutive e • Progressione radiologica da confermare con 2 scansioni a 4-12 settimane di distanza. Se la progressione è accompagnata da nuovi sintomi o deterioramento del performance status non attribuito a tossicità, è sufficiente una sola scansione. • La progressione deve avvenire durante il trattamento con il regime anti-PD1 approvato per il melanoma o entro 6 mesi dall’interruzione dell’anti-PD1, e indipendentemente da qualsiasi terapia interventistica. • Performance status ECOG (Eastern Cooperative Oncology Group (PS) =1. • I pazienti devono avere la lattato deidrogenasi sierica (LDH) = ULN.
Fare riferimento al protocollo per una descrizione completa dei criteri di inclusione. |
|
E.4 | Principal exclusion criteria |
• History of uveal, acral, or mucosal melanoma. • Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related adverse events (irAEs). Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included. • Systemic immune suppression within 14 days prior to randomization: - Use of chronic systemic steroid medication (up to 5 mg/day prednisolone equivalent is allowed); patients using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible, - Other clinically relevant systemic immune suppression.
Please refer to the protocol for a full description of the exclusion criteria. |
• Anamnesi di melanoma uveale, acrale o mucosale. • Evidenza in corso o recente (entro almeno 5 anni) di malattia autoimmune significativa che richiede trattamento con terapie immunosoppressive sistemiche, che potrebbe porre il rischio di eventi avversi immuno-correlati (irAE). Nota: Pazienti con ipertiroidismo autoimmune, ipotiroidismo autoimmune che sono in remissione, o con dose stabile di ormone tiroideo sostitutivo, vitiligine, o psoriasi, possono essere inclusi. • Immunosoppressione sistemica entro 14 giorni prima della randomizzazione: - Uso cronico di steroidi sistemici (sono concessi fino a 5 mg/die di equivalente di prednisolone); sono idonei i pazienti che usano dosi sostitutive fisiologiche di prednisolone per insufficienza adrenergica o ipofisaria - Altra immunosoppressione sistemica clinicamente rilevante.
Fare riferimento al protocollo per una descrizione completa dei criteri di esclusione. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response by blinded independent central review (BICR). |
ORR è definito come proporzione di pazienti in cui si osserva una risposta completa (CR) o una risposta parziale (PR) come migliore risposta complessiva mediante revisione centrale indipendente (BICR). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Blinded centralized review and response assessment according to RECIST 1.1/iRECIST will take place on a continuous basis. • Assessment of Health Related Quality of Life will be done on a continuous bases at pre-specified time points |
La revisione centralizzata indipendente in cieco e la valutazione della risposta secondo i criteri RECIST 1.1/iRECIST avverranno su base continua. La valutazione della qualità della vita correlata alla salute avverrà su base continua a intervalli temporali pre-specificati |
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E.5.2 | Secondary end point(s) |
• ORR defined as the proportion of patients in whom a CR or PR is observed as best overall response by BICR. • Duration of response (DOR) defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (progressive disease, PD) by BICR or death from any cause (whichever occurs first). • Disease control rate (DCR) defined as the proportion of patients in whom a CR, PR or stable disease (SD; assessed at least 6 weeks after first dose) is observed as best overall response by BICR. • Time to response (TTR) defined as the time from randomization to the first objective tumor response (CR or PR) by BICR. • Progression-free survival (PFS) defined as the time from randomization to first objective tumor progression (PD) by BICR or death from any cause (whichever occurs first). • ORR, DOR, DCR, TTR, PFS, as assessed by the investigator. • Overall survival (OS) defined as the time from randomization to death from any cause • Occurrence of treatment-emergent adverse events (TEAE) within a patient including Grade =3 serious and/or fatal TEAE by relationship. • Occurrence of immune-related adverse events (irAE). • Occurrence of dose reduction and discontinuation of trial treatment within a patient due to TEAE. • Changes in laboratory parameters compared to baseline. • Occurrence of abnormal laboratory parameters within a patient. • Changes in vital signs parameters compared to baseline. • Occurrence of abnormal vital signs parameters within a patient. • Mean changes from baseline in the global health status score of the EORTC- QLQ-C30 • Mean changes from baseline in scores of the EORTC QLQC30 functional and symptoms scales • Time to first clinically meaningful deterioration in global health status score as measured by EORTC QLQ-C30 • Time to first clinically meaningful deterioration in symptoms and functioning as measured by EORTC QLQ-C30 |
• ORR è definito come proporzione di pazienti in cui si osserva una CR o una PR come migliore risposta complessiva mediante BICR. • Durata della risposta (DOR) definita come il tempo dalla prima risposta obiettiva (CR o PR) alla prima incidenza di progressione tumorale obiettiva (progressione della malattia, PD) mediante BICR o decesso per qualunque causa (in base a quale evento si verifica per primo). • Tasso di controllo della malattia (DCR) definito come proporzione di pazienti in cui si osserva una CR, PR o malattia stabile (SD; valutata ad almeno 6 settimane dopo la prima dose) come risposta migliore complessiva mediante BICR. • Tempo alla risposta (TTR) definito come il tempo dalla randomizzazione alla prima risposta tumorale obiettiva (CR o PR) mediante BICR. • Sopravvivenza libera da progressione (PFS) definita come il tempo dalla randomizzazione alla prima progressione tumorale obiettiva (PD) mediante BICR o decesso per qualunque causa (in base a quale evento si verifica per primo). • ORR, DOR, DCR, TTR, PFS, valutato dallo sperimentatore. • Sopravvivenza complessiva (OS) definita come il tempo dalla randomizzazione al decesso per qualsiasi causa. • Incidenza di eventi avversi emergenti dal trattamento (TEAE) in un paziente compresi TEAE di Grado =3, seri e/o fatali mediante relazione. • Incidenza di eventi avversi immuno-correlati (irAE). • Incidenza di riduzione della dose e interruzione del trattamento della sperimentazione in un paziente dovuta a TEAE. • Cambiamento dei parametri di laboratorio rispetto al basale. • Incidenza di parametri di laboratorio anormali in un paziente. • Cambiamento dei parametri vitali rispetto al basale. • Incidenza di parametri vitali anormali in un paziente. • Media dei cambiamenti rispetto al basale nel punteggio dello stato di salute globale misurato secondo i criteri di EORTC QLQ-C30. • Media dei cambiamenti rispetto al basale nei punteggi delle scale funzionali e sintomatiche di EORTC QLQ-C30. • Tempo al primo deterioramento clinicamente significativo nel punteggio dello stato di salute globale misurato secondo i criteri di EORTC QLQ-C30. • Tempo al primo deterioramento clinicamente significativo nei sintomi e nelle funzionalità misurato secondo i criteri di EORTC QLQ-C30. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Blinded centralized review and response assessment according to RECIST 1.1/iRECIST will take place on a continuous basis. • DOR defined as the time from first objective response (CR/PR) to first occurrence of objective tumor progression (progressive disease, PD) by BICR or death from any cause. • DCR defined as the proportion of patients in whom a CR, PR or stable disease (SD; assessed at least 6 weeks after first dose) is observed as best overall response by BICR. • TTR defined as the time from randomization to the first objective tumor response (CR or PR) by BICR. • PFS defined as the time from randomization to first objective tumor progression (PD) by BICR or death from any cause. •OS defined as the time from randomization to death from any cause. |
• La revisione centralizzata indipendente in cieco e la valutazione della risposta secondo i criteri RECIST 1.1/iRECIST avverranno su base continua. • DOR definita come il tempo tra la prima risposta obiettiva (CR/PR) e la prima comparsa di PD secondo BICR o il decesso per qualsiasi causa. • DCR definito come % di pazienti in cui si osserva una CR, PR o SD (valutata ad almeno 6 settimane dalla prima dose) quale migliore risposta globale secondo BICR. •TTR definito come il tempo che intercorre tra la randomizzazione e la prima CR o PR secondo BICR. •PFS definita il tempo che intercorre tra la randomizzazione e la prima PD secondo BICR o il decesso per qualsiasi causa. •OS definita come il tempo che intercorre tra la randomizzazione e il decesso per qualsiasi causa. |
|
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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Australia |
United States |
France |
Germany |
Italy |
Poland |
Spain |
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 end of the trial will be declared at the time at which: • all patients have discontinued trial treatment; and • all patients have completed safety follow-up assessment at day 90 subsequent to last dose; and • all patients have been followed-up for at least 24 months subsequent to first dose or • the sponsor discontinues the trial. |
La fine dello studio verrà dichiarata nel momento in cui: •tutti i pazienti avranno sospeso il trattamento dello studio; e •tutti i pazienti avranno completato la valutazione di follow-up della sicurezza al giorno 90 successivo all’ultima dose; e •tutti i pazienti sono stati seguiti per almeno 24 mesi successivi dopo la prima dose oppure •il promotore sospende lo studio. |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |