E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Untreated Metastatic or Unresectable Melanoma |
Melanoma metastásico o irresectable no tratado previamente |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Melanoma |
Melanoma avanzado |
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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 | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 100000004864 |
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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 | 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 |
Phase 3 portion of the trial - To compare progression-free survival (PFS) of BMS-986213 to nivolumab monotherapy in participants with previously untreated, unresectable or metastatic melanoma.
Phase 2 portion of the trial - To compare the overall-response rate (ORR) of BMS-986213 to nivolumab monotherapy in participants with unresectable or metastatic melanoma. |
Parte de la Fase 3 del estudio - comparar la supervivencia libre de progresión (SLP) con BMS-986213 con respecto a la obtenida con nivolumab en monoterapia en pacientes con melanoma irresecable o metastásico no tratado previamente, Parte de la Fase 2 del estudio - comparar la Tasa de respuesta global (TRO) con BMS-986213 con la obtenida con nivolumab monoterapia en pacientes con melanoma irresecable o metastásico |
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E.2.2 | Secondary objectives of the trial |
Phase 3 portion of the trial - To compare overall survival (OS) of BMS-986213 to nivolumab o in subjects with with previously untreated, unresectable or metastatic melanoma - To compare ORR of BMS-986213 to nivolumab in subjects with unresectable or metastatic melanoma
Phase 2 portion of the trial Among subjects with unresectable or metastatic melanoma treated with BMS-986213 and those treated with nivolumab monotherapy: - To estimate the treatment effect, measured by ORR, as determined by BICR using RECISTv1.1, in subgroups based on combinations of LAG-3 expression and PDL-1 status - To evaluate DOR, DCR, PFS rates at pre-specified time points based on BICR assessments using RECIST v1.1 in the randomized population and in subgroups based on combinations of LAG-3 expression and PDL-1 status - To assess the 1- and 2-year landmark OS in the randomized population and in subgroups based on combinations of LAG-3 expression and PDL-1 status - To assess safety and tolerability |
Fase 3 : - comparar SG con BMS-986213 con la obtenida con nivo en monoterapia en pacien. con melanoma irresecable o metastásico no tratado previamente, - comparar la TRO con BMS-986213 con la obtenida con nivo en monote. en pacien. con melanoma irresecable o metastásico. Fase 2: Entre los pacien. con melanoma irresecable o metastásico tratados con BMS-986213 y aquellos tratados con nivo en monoter.: - Estimar el efecto del tratamiento, medido mediante la TRO, determinado por RCIE usando RECISTv1.1, en subgrupos basados en combinaciones de expresión LAG-3 y estado de PDL-1. - Evaluar tasas de DdR, TCE y tasas SLP en momentos de tiempo preespecificados de acuerdo con las evaluaciones RCIE usando RECIST v1.1 en la población aleatorizada y en subgrupos basados en la combinación de expresión de LAG-3 y estado de PDL-1. - Evaluar SG de 1 y 2 años en la población aleatorizada y en subgrupos basados en combinaciones de expresión de LAG-3 y estado de PDL-1. - Evaluar seguridad y tolerabilidad. |
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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 |
See protocol Section 9.8.2.7.: Additional Research Collection |
Consultar la secdción 9.8.2.7 (Colección adicional de investigación) del protocolo |
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E.3 | Principal inclusion criteria |
- Participants must have histologically confirmed Stage III (unresectable) or Stage IV melanoma, per the AJCC staging system - Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma - Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses |
- Los participantes deben tener melanoma confirmado histológicamente en estadio III (irresecable) o en estadio IV, según el sistema de estadificación del AJCC - Los participantes no deben haber recibido tratamiento oncológico sistémico previo para melanoma irresecable o metastásico - Debe facilitarse tejido tumoral de una localización irresecable o metastásico de la enfermedad para análisis de biomarcadores |
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E.4 | Principal exclusion criteria |
- Participants must not have active brain metastases or leptomeningeal metastases - Participants must not have ocular melanoma - Participants must not have an active, known, or suspected autoimmune disease |
Metástasis cerebrales activas o metástasis leptomeníngeas
Melanoma ocular
Participantes con enfermedad autoinmune activa, conocida o sospechada |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome Measures: 1/ Progression Free Survival (PFS) Phase 3 portion of trial. Assessed by a Blinded Independent Central Review (BICR) 2/ Overall Response Rate (ORR) Phase 2 portion of trial, assessed by a BICR |
Medidas primarias de resultados: 1 / Supervivencia libre de progresión (SLP) Fase 3 del ensayo. Evaluada por una Revisión Central Independiente Enmascarada (RCIE) 2 / Tasa de respuesta objetiva (TRO) Fase 2 del ensayo, evaluada por un RCIE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: 1/ Up to 5 years 2/ Up to 5 years |
Periodo de tiempo: 1 / hasta 5 años 2 / hasta 5 año |
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E.5.2 | Secondary end point(s) |
Secondary outcome measures: 1/ Overall Survival (OS) Phase 3 portion of trial. To compare BMS-986213 to nivolumab monotherapy 2/ ORR Phase 3 portion of trial, assessed by a BICR 3/ ORR Phase 2 portion of trial, assessed by a BICR in subgroups 4/ Duration of Response (DOR) Phase 2 portion of trial. In the randomized population and in subgroups 5/ Disease Control Rate (DCR) Phase 2 portion of trial. In the randomized population and in subgroups 6/ PFS Phase 2 portion of trial. In the randomized population and in subgroups 7/ OS Phase 2 portion of trial. In the randomized population and in subgroups 8/ Number of Adverse Events (AEs) Phase 2 portion of the trial 9/ Number of Serious Adverse Events (SAEs) Phase 2 portion of the trial 10/ Number of AEs Leading to Discontinuation Phase 2 portion of the trial 11/ Number of Deaths Phase 2 portion of the trial 12/ Number of Laboratory Abnormalities Phase 2 portion of the trial |
Medidas de resultado secundarias: 1 / Supervivencia global (SG) Fase 3 del estudio. Para comparar BMS-986213 con nivolumab monoterapia 2 / TRO tasa respuesta objetiva Fase 3 del estudio, evaluada por un RCIE 3 / TRO tasa respuesta objetiva Fase 2 del estudio, evaluada por un RCIE en subgrupos 4 / Duración de la respuesta (DdR) Fase 2 del estudio. En la población aleatorizada y en subgrupos 5 / Tasa de control de enfermedades (TCE) Fase 2 del estudio. En la población aleatorizada y en subgrupos 6 / SLP Fase 2 del estudio. En la población aleatorizada y en subgrupos 7 / SG Fase 2 del estudio. En la población aleatorizada y en subgrupos 8 / Cantidad de eventos adversos (EA) Fase 2 del estudio 9 / Número de eventos adversos graves (EAG) Fase 2 del estudio 10 / Cantidad de eventos adversos que conducen a la interrupción Fase 2 del estudio 11 / Número de muertes Fase 2 del estudio 12 / Número de anomalías en el laboratorio Fase 2 del estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ Time Frame: Up to 5 years 2/ Time Frame: Up to 5 years 3/ Time Frame: Up to 5 years 4/ Time Frame: Up to 5 years 5/ Time Frame: Up to 5 years 6/ Time Frame: Up to 5 years 7/ Time Frame: Up to 5 years 8/ Time Frame: Up to 5 years 9/ Time Frame: Up to 5 years 10/ Time Frame: Up to 5 years 11/ Time Frame: Up to 5 years 12/ Time Frame: Up to 5 years |
1 / Marco de tiempo: hasta 5 años 2 / Marco de tiempo: hasta 5 años 3 / Marco de tiempo: hasta 5 años 4 / Marco de tiempo: hasta 5 años 5 / Marco de tiempo: hasta 5 años 6 / Marco de tiempo: hasta 5 años 7 / Marco de tiempo: hasta 5 años 8 / Marco de tiempo: hasta 5 años 9 / Marco de tiempo: hasta 5 años 10 / Marco de tiempo: hasta 5 años 11 / Marco de tiempo: 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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Chile |
Colombia |
Denmark |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Norway |
Poland |
Romania |
Russian Federation |
Spain |
Sweden |
Taiwan |
United Kingdom |
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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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 1 |