E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H) |
Tumores sólidos avanzados o metastásicos con alta carga mutacional (TMB-H) |
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E.1.1.1 | Medical condition in easily understood language |
refractory, metastatic, or unresectable Tumor Mutational Burden-High solid tumors (except melanoma, non-small cell lung cancer, renal cell carcinoma or hematological malignancy) |
Tumores sólidos avanzados, refractarios, metastásicos o irresecables con alta carga mutacional (excepto melanoma, cáncer de pulmón no microcitico, cáncer renal y neoplasias hematologicas) |
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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 | 10065252 |
E.1.2 | Term | Solid tumor |
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 |
-To compare BICR-assessed objective response rate (ORR) in participants of tTMB-H treated with nivolumab combined with ipilimumab with a historical control -To compare BICR-assessed ORR in participants of bTMB-H treated with nivolumab combined with ipilimumab with a historical control |
-Comparar la tasa de respuestas objetivas (TRO) evaluadas mediante RCIE en pacientes con tTMB-H tratados con nivolumab combinado con ipilimumab con un control histórico -Comparar la TRO evaluada por RCIE en pacientes con bTMB-H tratados con nivolumab combinado con ipilimumab con un control histórico |
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E.2.2 | Secondary objectives of the trial |
To assess: - BICR-assessed duration of response (DOR) and time to response (TTR) in tTMB-H or bTMB-H patients treated with nivo + ipi - BICR-assessed ORR, DOR and TTR in tTMB-H or bTMB-H patients treated with nivo alone - Investigator-assessed ORR, DOR, TTR in tTMB-H or bTMB-H patients treated with nivo + ipi and nivo alone - BICR- and investigator-assessed clinical benefit rate (CBR) in tTMB-H or bTMB-H patients treated with nivo + ipi and nivo alone - BICR- and investigator-assessed progression free survival (PFS) in tTMB-H or bTMB-H patients treated with nivo + ipi and nivo alone - Overall Survival (OS) in tTMB-H or bTMB-H patients treated with nivo +ipi and nivo alone - overall safety and tolerability |
-Estimar duración de respuesta (DdR) y tiempo hasta respuesta (THR) valorados mediante RCIE en pacientes con tTMB-H o bTMB-H tratados con nivo combinado con ipi. -Estimar tasa respuesta objetiva (TOR), DdR y THR evaluados mediante RCIE en pacientes con tTMB-H o bTMB-H tratados con nivo en monoterapia. -Evaluar TRO, DdR y THR en pacientes con tTMB-H o bTMB-H tratados con nivo en combinación con ipili y nivo en monoterapia.-Evaluar tasa de beneficio clínico (TBC) valorada mediante RCIE y valorada por el investigador en pacientes con tTMB-H o bTMB-H tratados con nivo en combinación con ipi y con nivo en monoterapia. -Evaluar supervivencia libre de progresión (SLP) valorada mediante RCIE y valorada por el investigador en pacientes con tTMB-H o bTMB-H tratados con nivo combinado con ipi y con nivo en monoterapia.-Evaluar supervivencia global (SG) en pacientes con tTMB-H o bTMB-H tratados con nivo combinado con ipili y con nivol en monoterapia.-Evaluar seguridad y tolerabilidad globales. |
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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 9.8.1 of the protocol. |
Este protocolo incluirá el almacenamiento de muestras residuales para investigación adicional (IA). Para más detalles, consulte la sección 9.8.1 del protocolo. |
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E.3 | Principal inclusion criteria |
- Refractory, metastatic, or unresectable TMB-H solid tumors who must have received at least one prior line of therapy including standard of care, if available - Available tumor tissue for TMB-H testing - Participants must have measurable disease for response assessment |
-Pacientes con tumores sólidos con TMB-H refractarios, metastásicos o irresecables que deben haber recibido al menos una línea de tratamiento previa, incluido el tratamiento de referencia, si lo hay. -Tejido tumoral disponible para pruebas TMB-H -Los pacientes deben tener enfermedad medible para la evaluación de la respuesta |
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E.4 | Principal exclusion criteria |
- Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease - Participants who received prior treatment with an anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways - Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment |
- Pacientes con melanoma, cáncer de pulmón no microcitico (CPNM), carcinoma de células renales (CCR) o neoplasias hematológicas como sitio primario de enfermedad - Pacientes que recibieron tratamiento previo con un anticuerpo anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137 o anti-CTLA-4 o cualquier otro anticuerpo o fármaco dirigido específicamente a la co-estimulación de células T. o vías de puntos de control - Tratamiento con cualquier quimioterapia, radioterapia, fármacos biológicos para el cáncer o tratamiento de investigación dentro de los 28 días de la primera administración del tratamiento del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
-BICR-assessed ORR using RECIST 1.1, and Response Assessment for Neuro-Oncology (RANO) criteria in primary CNS tumors -BICR-assessed ORR using RECIST 1.1, and RANO criteria in primary CNS tumors |
-TRO evaluada por RCIE según los RECIST 1.1 y los criterios de Evaluación de la Respuesta en Neurooncología (RANO) en tumores primarios del SNC -TRO evaluada por RCIE según los RECIST 1.1 y los criterios RANO en tumores primarios del SNC |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 3 years |
Aproximadamente 3 años |
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E.5.2 | Secondary end point(s) |
-BICR-assessed DOR -BICR-assessed TTR -BICR-assessed ORR -Investigator-assessed ORR -Investigator-assessed DOR -Investigator-assessed TTR -BICR-assessed CBR -Investigator-assessed CBR -BICR-assessed PFS -Investigator-assessed PFS -Overall survival -AEs, clinical laboratory values, or other safety biomarkers |
DdR evaluado mediante RCIE THR evaluado mediante RCIE TRO evaluado mediante R DdR evaluado por el investigador THR evaluado por el investigador TRO evaluado por el investigador TBC evaluada mediante RCIE TBC evaluada por el investigador PFS evaluada mediante RCIE PFS evaluada por el investigador Supervivencia global AAs, valores de laboratorio clínico u otros biomarcadores de seguridad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 3 years |
Aproximadamente 3 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers, Patient Reported Outcomes |
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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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Belgium |
Canada |
Chile |
Denmark |
France |
Germany |
Italy |
Netherlands |
Norway |
Poland |
Romania |
Singapore |
Spain |
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
|
End of trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last participant (last follow-up visit of last participant). |
El final del ensayo se define como la última visita del paciente o procedimiento programado que se muestra en el programa de actividades para el ultimo paciente (última visita de seguimiento del ultimo 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 | 4 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |