E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population will include participants with 1 of the following advanced or metastatic tumors approved for treatment with nivolumab monotherapy: non-small cell lung cancer (NSCLC); renal cell carcinoma (RCC); unresectable or metastatic melanoma; hepatocellular carcinoma (HCC); and microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC). |
La población del ensayo incluirá a pacientes con 1 de los siguientes tipos de tumores avanzados o metastásicos en los que está aprobado el tratamiento con nivolumab en monoterapia: CPNM; carcinoma de células renales (CCR); melanoma irresecable o metastásico. Se incluyen además carcinoma hepatocelular (CHC) y cáncer colorrectal con inestabilidad de microsatélites alta o déficit de reparación de discordancias (CRC MSI-H/dMMR) que no están aprobados en la Unión Europea. |
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E.1.1.1 | Medical condition in easily understood language |
lung cancer; kidney cancer; melanoma; liver cancer; colorectal cancer |
Cáncer de pulmón, cáncer de riñón; melanoma; cáncer de hígado; cáncer colorrectal |
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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 | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10061451 |
E.1.2 | Term | Colorectal cancer |
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 describe the pharmacokinetics of nivolumab administered subcutaneously, with or without rHuPH20 |
Describir la farmacocinética de nivolumab administrado por vía subcutánea, con o sin rHuPH20 |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety profile of SC nivolumab - To evaluate incidence of AEs in the broad scope MedDRA Anaphylactic Reaction SMQ and the select AE hypersensitivity/infusion reaction category - To assess the immunogenicity of nivolumab |
Evaluar el perfil de seguridad de nivolumab SC. Evaluar la incidencia de AA en SMQ en el ámbito general de la Reacción Anafiláctica y en la categoría de AA seleccionados de hipersensibilidad/reacción a la perfusión. Evaluar la inmunogenicidad de nivolumab |
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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 |
This protocol will include residual sample storage for additional research (AR). For more details please refer to section 9.8.3 of the study protocol. |
Este protocolo incluirá el almacenamiento de muestras residuales para investigaciones adicionales. Para más detalles, ver la sección 9.8.3 del protocolo de este ensayo. |
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E.3 | Principal inclusion criteria |
- Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types: 1) Metastatic squamous or non-squamous NSCLC 2) Renal Cell Carcinoma, advanced or metastatic 3) Melanoma 4) Hepatocellular Carcinoma 5) Colorectal Cancer, metastatic (MSI-H or dMMR) - Measurable disease as per RECIST version 1.1 criteria - ECOG performance status of 0 or 1 |
Tumores sólidos avanzados (metastásicos y/o irresecables) histológica o citológicamente confirmados, de los siguientes tipos: 1) CPNM metastásico, escamoso o no-escamoso 2) Cáncer de células renales avanzado o metastásico 3) Melanoma 4) Carcinoma Hepatocelular 5) cáncer colorrectal con inestabilidad de microsatélites alta o déficit de reparación de discordancias (CRC MSI-H/dMMR) - Enfermedad medible por criterios RECIST versión 1.1 - ECOG de 0 o 1 |
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E.4 | Principal exclusion criteria |
- Active brain metastases or leptomeningeal metastases - Ocular melanoma - Active, known, or suspected autoimmune disease |
Metástasis cerebrales activas o metástasis leptomeníngeas - melanoma ocular - Enfermedad autoinmune conocida o sospechada |
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E.5 End points |
E.5.1 | Primary end point(s) |
Serum nivolumab: -Cmax (Maximal concentration) -Tmax (Time to maximal concentration) -AUC(TAU) (Area under the concentration-time curve in one dosing interval) -Ctau (observed serum nivolumab concentration at the end of the dosing interval) |
Nivolumab sérico: -Cmax (Concentración máxima) -Tmax (Tiempo hasta la concentración máxima) -AUC(TAU) (Área bajo la curva concentración-tiempo en un intervalo de dosis) -Ctau (concentración de nivolumab sérica observada al final del intervalo de dosis) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For all primary endpoints: approximately 1 year after Last Patient First Treatment |
Para todos los criterios de valoración principales: aproximadamente 1 año después del primer tratamiento del último paciente |
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E.5.2 | Secondary end point(s) |
- Incidences of AEs, SAEs, AEs leading to discontinuation, deaths, and laboratory abnormalities - Incidence of AEs in the MedDRA Anaphylactic Reaction broad scope SMQ occurring within 2 days after study drug administration - Incidence of events within the hypersensitivity/infusion reaction select AE category occurring within 2 days after any study drug administration. - Incidence of anti-nivolumab antibodies and neutralizing antibodies, if applicable |
- Incidencias de AA, AAG, AA que conducen a suspensión, muertes y anomalías de laboratorio. - Incidencia de AA en SMQ en el ámbito general de la Reacción Anafiláctica del MedDRA que se producen en el plazo de 2 días después de la administración del fármaco del estudio. -Incidencia de acontecimientos dentro de la categoría de AA seleccionados de hipersensibilidad/reacción a la perfusión que se producen dentro del plazo de 2 días después de la administración de algún fármaco del estudio. - Incidencia de anticuerpos anti-nivolumab y anticuerpos neutralizadores, si procede. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all secondary endpoints: approximately 2 years after Last Patient First Treatment |
Para todos los criterios de valoración secundarios: aproximadamente 2 años después del primer tratamiento del último paciente |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Experience and Preference Questionnaire |
Cuestionario con la experiencia y preferencias del paciente |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
pharmacokinetics (PK), safety, and tolerability of nivolumab SC with or without rhuPh20 |
Framacocinética (FC), seguridad, tolerabilidad de Nivolumab SC con o sin rhuPh20 |
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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 | No |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Chile |
France |
Italy |
New Zealand |
Poland |
Spain |
United States |
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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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End of trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last participant (=last survival follow-up visit of the last participant) |
El fin de ensayo se define la última visita o procedimiento programado que se muestre en la programación de actividades para el último participante (=última visita de seguimiento de supervivencia del último participante) |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 1 |