E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated unresectable or metastatic melanoma |
Melanoma irresecable o metastásico no tratado |
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E.1.1.1 | Medical condition in easily understood language |
Untreated inoperable or metastatic melanoma |
Melanoma inoperable o metastásico no tratado |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The purpose of this study is to determine whether an investigational immunotherapy NKTR-214, when combined with nivolumab, is more effective than nivolumab by itself in participants with unresectable or metastatic melanoma that is previously untreated |
El objetivo de este estudio es determinar si la inmunoterapia en investigación NKTR-214, cuando se combina con nivolumab, es más eficaz que nivolumab solo en pacientes con melanoma irresecable o metastásico previamente no tratado |
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E.2.2 | Secondary objectives of the trial |
- To evaluate efficacy of NKTR-214 combined with nivolumab and that of nivolumab monotherapy - To evaluate the association between PD-L1 tumor expression on tumor cells (≥ 1% or < 1%/indeterminate) and efficacy measures including PFS and ORR by BICR and OS. -To evaluate the safety and tolerability of NKTR-214 combined with nivolumab and that of nivolumab monotherapy |
- Evaluar la eficacia de NKTR-214 en combinación con nivolumab y la de nivolumab en monoterapia - Evaluar la asociación entre la expresión de PD-L1 en las células tumorales (≥ 1% o < 1%/indeterminada) y medidas de eficacia, incluida la SLP y la TRO mediante RCIE y la SG - Evaluar la seguridad y la tolerabilidad de NKTR-214 en combinación con nivolumab y la de nivolumab en monoterapia |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Additional Research Collection - see protocol section 9.8.1 This protocol will include residual sample storage for additional research (AR). AR is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements. This collection for additional research is intended to expand the translational R&D capability at Bristol- Myers Squibb, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc. |
Recogida de muestras adicional para investigación - ver la sección 9.8.1 del protocolo Este protocolo incluye la conservación de muestras residuales para investigación adicional. La investigación adicional es opcional para todos los participantes del estudio, excepto donde la retención y/o recogida está prohibida por legislación local, comités éticos o requerimientos institucionales. Esta recogida para la investigación adicional tiene como objetivo expandir la capacidad translacional de I+D en Bristol-Myers Squibb, y apoyará objetivos de investigación aún no definidos que fomentarán nuestra comprensión de la enfermedad y las opciones de tratamiento. También se podrá utilizar para apoyar las solicitudes de análisis de las autoridades sanitarias, y el avance del desarrollo farmacodiagnóstico para orientar mejor los fármacos hacia los pacientes adecuados. Esto también puede incluir la exploración genética/genómica dirigida a explorar las vías de la enfermedad, la progresión y la respuesta al tratamiento, etc. |
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E.3 | Principal inclusion criteria |
- Eastern Cooperative Oncology Group (ECOG) performance status of </=1 (adults 18 years or older)/ Lansky Performance Score >/= 80% (minors ages 12-17 only) - Histologically confirmed stage III (unresectable) or stage IV melenoma - Treatment-naive participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant treatment |
- Estado funcional del Eastern Cooperative Oncology Group (ECOG) </= 1 (adultos de 18 años o más)/ Puntuación de estado funcional de Lansky >/= 80% (en menores, solo edades de 12-17 años). - Melanoma confirmado histológicamente, en estadio III (irresecable) o estadio IV - Pacientes sin tratamiento previo (es decir, ningún tratamiento sistémico previo contra el melanoma irresecable o metastásico) a excepción de tratamiento adyuvante previo. |
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E.4 | Principal exclusion criteria |
- Active brain metastases or leptomeningeal metastases - Uveal melanoma - Participants with an active, known or suspected autoimmune disease |
- Metástasis cerebrales activas o metástasis leptomeníngeas. - Melanoma uveal - Pacientes con enfermedad autoinmune activa, conocida o sospechada |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Overall response rate (ORR) by Blinded Independent central review (BICR) - Progression-free survival (PFS) by BICR - Overall survival (OS) |
- Tasa de respuesta objetiva (TRO) mediante revisión central independiente enmascarada (RCIE) - Supervivencia libre de progresión (SLP) mediante RCIE - Supervivencia global (SG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 5 years |
Hasta 5 años |
|
E.5.2 | Secondary end point(s) |
- Clinical Benefit Rate (CBR) by BICR - Duration of Response (DoR) by BICR - Duration of overall Complete Response (DoCR) by BICR - Time To Response (TTR) by BICR - ORR by investigator - PFS by investigator - CBR by investigator - DoR by investigator - DoCR by investigator - TTR by investigator - PFS per BICR in biomarker population - ORR per BICR in biomarker population - OS in biomarker population - Incidence of Adverse Events (AEs) - Incidence of treatment-related AEs - Incidence of Serious Adverse Events (SAEs) - Incidence of treatment-related SAEs - Incidence of laboratory abnormalities |
- Tasa de beneficio clínico (TBC) mediante RCIE - Duración de la respuesta (DdR) mediante RCIE - Duración de la respuesta completa (DdRC) mediante RCIE - Tiempo hasta la respuesta (THR) mediante RCIE - TRO evaluada por el investigador - SLP evaluada por el investigador - TBC evaluada por el investigador - DdR evaluada por el investigador - DdRC evaluada por el investigador - THR evaluada por el investigador - SLP mediante RCIE en la población de biomarcadores - TRO mediante RCIE en la población de biomarcadores - SG en la población de biomarcadores - Incidencia de acontecimientos adversos (AAs) - Incidencia de AAs relacionados con el tratamiento - Incidencia de acontecimientos adversos graves (AAGs) - Incidencia de AAGs relacionados con el tratamiento - Incidencia de anomalías de laboratorio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 5 years |
Hasta 5 años |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
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 | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Switzerland |
United Kingdom |
United States |
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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
|
LVLS |
Última visita del ultimo paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |