E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Previously Untreated Unresectable or Metastatic Melanoma |
Sujetos con melanoma irresecable o metastásico no tratado previamente |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 | 19.0 |
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 primary objective is to evaluate the difference in safety between the FRC product (BMS-986214) relative to sequentially administered nivolumab 1 mg/kg and ipilimumab 3 mg/kg as measured by the incidence of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ occurring within 2 days after dosing during the combination, Part 1 period in subjects with previously untreated, unresectable or metastatic melanoma. |
El objetivo principal es evaluar la diferencia en la seguridad entre el producto de FRC (Fixed Ratio Combination) (BMS-986214) en relación con Nivolumab 1 mg/kg e Ipilimumab 3 mg/kg administrados secuencialmente, medido por la incidencia de AA (Acontecimientos Adversos) según el SMQ de amplio alcance de reacciones anafilácticas del MedDRA que se produzcan dentro del plazo de 2 días después de la administración durante el periodo de combinación, la Parte 1, en sujetos con melanoma irresecable o metastásico no tratado previamente. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives include: -To evaluate incidence of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ and the select AE hypersensitivity/infusion reaction category -To evaluate Grade 3 - 5 AE incidence rate (drug-related and all causality) defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria -To determine PK comparisons of nivolumab and ipilimumab administered as FRC to that of sequentially administered nivolumab and ipilimumab -To evaluate the objective response rate (ORR), as determined by investigators -To evaluate progression free survival (PFS) |
Los objetivos secundarios clave incluyen: - Evaluar la incidencia de AA según el SMQ (Formulario estándar MedDRA) de alcance restringido de reacciones anafilácticas del MedDRA y la categoría seleccionada de AA de hipersensibilidad/reacción a la perfusión - Evaluar la tasa de incidencia de AA de grado 3 - 5 (relacionados con el fármaco y de todas las causas) definida usando los Criterios de Terminología Común de Acontecimientos Adversos del National Cancer Institute (CTCAE-NCI) versión 4.0 - Determinar las comparaciones de FC (Farmacocinética) de Nivolumab e Ipilimumab administrados en FCR con la de Nivolumab e Ipilimumab administrados secuencialmente - Evaluar la tasa de respuestas objetivas (TRO), determinada por los investigadores - Evaluar la supervivencia libre de progresión (SLP) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males and Females, ages >= 15 years of age (Except where local regulations and/or institutional policies do not allow for subjects < 18 years of age to participate.) - Subjects must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma that is unresectable or metastatic - Eastern Cooperative Oncology Group (ECOG) performance status of 01 - Subjects have not been treated by systemic anticancer therapy for unresectable or metastatic melanoma |
- Hombres y mujeres, edades >= 15 años (excepto cuando las normas locales y/o las políticas del centro no permitan que participen sujetos < 18 años) - Los sujetos deben tener melanoma irresecable o metastásico, en estadio III o IV histológicamente confirmado - Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0-1 -Pacientes que no se hayan sometido a ningún tratamiento oncológico sistémico previo para melanoma irresecable o metastásico. |
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E.4 | Principal exclusion criteria |
- Subjects with active brain metastases or leptomeningeal metastases - Subjects with ocular melanoma - Subjects with active, known or suspected autoimmune disease |
- Sujetos con metástasis cerebrales activas o metástasis leptomeníngeas. - Sujetos con melanoma ocular - Sujetos con enfermedad autoinmune activa, conocida o sospechada. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the incidence of adverse events in anaphylactic reaction SMQ (broad scope) |
El objetivo primario del estudio es la incidencia de Acontecimientos Adversos de SMQ de reacción anafiláctica |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis will occur when all subjects who are still on-treatment have had at least 2 post-baseline tumor assessments (~20 weeks). |
El análisis del objetivo primario se producirá cuando todos los sujetos que sigan en tratamiento hayan tenido al menos 2 evaluaciones tumorales post-basales. |
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E.5.2 | Secondary end point(s) |
- Incidence of adverse events in anaphylactic reaction SMQ (narrow scope) - The incidence of events within the hypersensitivity/infusion reaction select AE category - Incidence of Grade 3-5 Adverse Events (AEs) - Objective Response Rate (ORR) - Progression Free Survival (PFS) - PK comparisons of study drug administered |
- Evaluar la incidencia de AA según el SMQ de alcance restringido de reacciones anafilácticas - Evaluar la incidencia de AA dentro categoría seleccionada de AA de hipersensibilidad/reacción a la perfusión - Evaluar la tasa de incidencia de AA de grado 3 - 5 - Evaluar la tasa de respuestas objetivas (TRO) - Evaluar la supervivencia libre de progresión (SLP) - Determinar las comparaciones de FC (Farmacocinética) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments |
Evaluaciones de biomarcadores y evaluaciones de investigación de resultados |
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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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Nivolumab e Ipilimumab administrados en una proporción fija versus secuencialmente |
Nivolumab and Ipilimumab administered in a Fixed Ratio Combination versus sequentially |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
Australia |
France |
Italy |
Spain |
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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
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Last follow-up visit of the last patient |
Última visita de seguimiento del último paciente |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |