- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT03743766
Nivolumab, BMS-936558 en combinación con Relatlimab, BMS-986016 en pacientes con melanoma metastásico sin tratamiento previo con inmunoterapia en el entorno metastásico
Un estudio de fase II del anticuerpo monoclonal anti-PD1 (Nivolumab, BMS-936558) administrado en combinación con el anticuerpo monoclonal anti-LAG3 (Relatlimab, BMS-986016) en pacientes con melanoma metastásico que no han recibido inmunoterapia previa en el entorno metastásico
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- UPMC Hillman Cancer Center
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Descripción
Criterios de inclusión:
• Hombres o mujeres de 18 años de edad o más que cumplan con los criterios de la octava edición del AJCC para melanoma irresecable en estadio IIIB, estadio IIIC, estadio IIID o estadio IV que no hayan recibido tratamiento con inmunoterapia en el entorno metastásico
Criterio de exclusión:
Metástasis del SNC conocidas o sospechadas, con las siguientes excepciones:
- Los sujetos con metástasis cerebrales controladas podrán inscribirse. Las metástasis cerebrales controladas se definen como ausencia de progresión radiográfica durante al menos 4 semanas después de la radiación o el tratamiento quirúrgico en el momento del consentimiento. Los sujetos deben estar sin esteroides durante al menos 2 semanas antes de la aleatorización.
- Los sujetos con signos o síntomas de metástasis cerebrales no son elegibles a menos que se descarten metástasis cerebrales mediante tomografía computarizada o resonancia magnética.
- Enfermedad autoinmune activa que requiera tratamiento, a excepción de diabetes mellitus tipo 1, vitíligo, asma/atopia infantil resuelta, hiper/hipotiroidismo controlado, hipoadrenalismo o hipopituitarismo.
- Tratamiento sistémico previo en el entorno metastásico, incluidos los anticuerpos anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA-4 o cualquier otro anticuerpo o fármaco que se dirija específicamente a la coestimulación de las células T o las vías del punto de control inmunitario; o quimioterapia.
- Tratamiento adyuvante previo con anticuerpo anti-PD1, anti-PDL1 y/o anti-LAG3. Tenga en cuenta que el tratamiento adyuvante previo con terapia dirigida (p. inhibición de BRAF/MEK), anti-CTLA4 o tratamiento no especificado anteriormente.
- Melanoma ocular
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Relatlimab
Ciclo 1: Relatlimab (BMS-986016) se suministra como una formulación estéril de 10 mg/ml para administrar como infusión intravenosa (IV) a 160 mg IV durante las primeras 4 semanas (ciclo 1). Ciclo 2+: la terapia combinada se administrará mediante infusión secuencial. Nivolumab administrado a 480 mg IV seguido de una infusión de relatlimab a 160 mg IV una vez cada 4 semanas. |
Relatlimab (BMS-986016): formulación de 10 mg/ml para administrar como infusión intravenosa (IV) a 160 mg IV.
Otros nombres:
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Experimental: Nivolumab
Ciclo 1: Nivolumab (BMS-936558) se suministra como una formulación estéril de 10 mg/mL para administrar como infusión IV a 480 mg IV durante las primeras 4 semanas. Ciclo 2+: la terapia combinada se administrará mediante infusión secuencial. Nivolumab administrado a 480 mg IV seguido de una infusión de relatlimab a 160 mg IV una vez cada 4 semanas. |
Nivolumab (BMS-936558): formulación de 10 mg/ml para administrar como infusión IV a 480 mg IV.
Otros nombres:
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Experimental: Relatlimab + Nivolumab
Ciclo 1+: la terapia combinada se administrará mediante infusión secuencial.
Nivolumab administrado a 480 mg IV seguido de una infusión de relatlimab a 160 mg IV durante las primeras 4 semanas (Ciclo 1), luego una vez cada 4 semanas.
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La terapia combinada (Relatlimab + Nivolumab) se administrará mediante infusión secuencial.
Nivolumab administrado a 480 mg IV seguido de una infusión de relatlimab a 160 mg IV.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
LAG3 Gene Expression From scRNAseq
Periodo de tiempo: At Baseline
|
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
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At Baseline
|
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LAG3 Gene Expression From scRNAseq
Periodo de tiempo: At Week 4
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Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
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At Week 4
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PD1 Expression
Periodo de tiempo: At baseline (Week 0)
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Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
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At baseline (Week 0)
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PD1 Expression
Periodo de tiempo: At Week 4
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Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
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At Week 4
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Change in Tumor Size
Periodo de tiempo: At baseline and at 4 weeks
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Percentage change in tumor size assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of:
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At baseline and at 4 weeks
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Overall Response Rate (ORR)
Periodo de tiempo: Beginning at 12 weeks post initial treatment, up to 4 years
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Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed.
Per RECIST v1.1, CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
(Note: the appearance of one or more new lesions is also considered progression).
SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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Beginning at 12 weeks post initial treatment, up to 4 years
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Overall Response Rate (ORR) - ITT (Intent-to-treat) Population
Periodo de tiempo: Beginning at 12 weeks post initial treatment, up to 4 years
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Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed.
Per RECIST v1.1, CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
(Note: the appearance of one or more new lesions is also considered progression).
SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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Beginning at 12 weeks post initial treatment, up to 4 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Duración de la respuesta
Periodo de tiempo: 12 semanas después del tratamiento inicial, hasta 4 años
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Tiempo desde la primera respuesta completa (RC) o respuesta parcial (PR) documentada hasta la primera fecha en que se documenta objetivamente la progresión de la enfermedad.
Según RECIST v1.1, CR: Desaparición de todas las lesiones diana.
Cualquier ganglio linfático patológico (ya sea objetivo o no objetivo) debe tener una reducción en el eje corto para
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12 semanas después del tratamiento inicial, hasta 4 años
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Supervivencia libre de progresión (PFS)
Periodo de tiempo: Hasta 4 años
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La supervivencia libre de progresión se define como el tiempo entre la fecha de aleatorización y la primera fecha de progresión documentada o muerte por cualquier causa, lo que ocurra primero.
Según RECIST v1.1, enfermedad progresiva (EP): al menos un 20 % de aumento en la suma de los diámetros de las lesiones diana, tomando como referencia la suma más pequeña del estudio (esto incluye la suma inicial si es la más pequeña del estudio).
Además del aumento relativo del 20%, la suma también debe demostrar un aumento absoluto de al menos 5 mm.
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Hasta 4 años
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Supervivencia general (SG)
Periodo de tiempo: Hasta 4 años
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La supervivencia global se define como el tiempo entre la fecha de aleatorización y la fecha de muerte por cualquier causa.
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Hasta 4 años
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Secondary Outcome: Clinical Benefit Rate
Periodo de tiempo: 12 weeks post initial treatment, up to 4 years
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Percent of patients with Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) / total patients assessed per RECIST v1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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12 weeks post initial treatment, up to 4 years
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Clinical Benefit Rate - ITT (Intent-to-treat) Population
Periodo de tiempo: 12 weeks post initial treatment, up to 4 years
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Percent of patients with Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) / total patients assessed per RECIST v1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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12 weeks post initial treatment, up to 4 years
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Progression-free Survival (PFS) by Lead-in Arm
Periodo de tiempo: Up to 4 years
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Progression-free survival is defined as the time between the date of randomization and the first date of documented progression or death due to any cause, whichever occurs first.
Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
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Up to 4 years
|
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CD8+ Tumor Infiltrating Lymphocytes
Periodo de tiempo: At Baseline
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Number of CD8+ tumor infiltrating lymphocytes present.
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At Baseline
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CD8+ Tumor Infiltrating Lymphocytes
Periodo de tiempo: At Week 4
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Number of CD8+ tumor infiltrating lymphocytes present.
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At Week 4
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CD4+ Tumor Infiltrating Lymphocytes
Periodo de tiempo: At Week 4
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Number of CD4+ tumor infiltrating lymphocytes present.
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At Week 4
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CD4+ Tumor Infiltrating Lymphocytes
Periodo de tiempo: At Baseline
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Number of CD4+ tumor infiltrating lymphocytes present.
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At Baseline
|
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LAG3 Levels - PBMC
Periodo de tiempo: At Baseline
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To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing.
The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
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At Baseline
|
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LAG3 Levels - PBMC
Periodo de tiempo: At Week 4
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To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing.
The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
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At Week 4
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LAG3 Levels - TIL
Periodo de tiempo: At Baseline
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To determine the amount of LAG3 expressed on activated tumor infiltrating lymphocytes (TIL) through single-cell RNA sequencing.
The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
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At Baseline
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LAG3 Levels - PBMC
Periodo de tiempo: At Week 16
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To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing.
The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
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At Week 16
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LAG3 Levels - TIL
Periodo de tiempo: At Week 4
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To determine the amount of LAG3 expressed on activated tumor infiltrating lymphocytes (TIL) through single-cell RNA sequencing.
The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
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At Week 4
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PD-1 Expression in PBMC
Periodo de tiempo: At Baseline
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To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients.
The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
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At Baseline
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PD-1 Expression in PBMC
Periodo de tiempo: At Week 4
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To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients.
The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
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At Week 4
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PD-1 Expression in PBMC
Periodo de tiempo: At Week 16
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To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients.
The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
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At Week 16
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PD-1 Expression in TIL
Periodo de tiempo: At Baseline
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To determine the amount of PD-1 (programmed cell death protein 1) expressed on TILs through single-cell RNA sequencing in treated patients.
The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
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At Baseline
|
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PD-1 Expression in TIL
Periodo de tiempo: At Week 4
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To determine the amount of PD-1 (programmed cell death protein 1) expressed on TILs through single-cell RNA sequencing in treated patients.
The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
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At Week 4
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Cell Effector/Memory Status - TIL
Periodo de tiempo: At Baseline
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Measure of cells that have previously encountered and responded to their cognate antigen in TIL.
|
At Baseline
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Cell Effector/Memory Status - TIL
Periodo de tiempo: At Week 4
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Measure of cells that have previously encountered and responded to their cognate antigen in TIL.
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At Week 4
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Cell Effector/Memory Status - PBMCs
Periodo de tiempo: At Baseline
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Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
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At Baseline
|
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Cell Effector/Memory Status - PBMC
Periodo de tiempo: At Week 4
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Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
|
At Week 4
|
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Cell Effector/Memory Status - PBMC
Periodo de tiempo: At Week 16
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Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
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At Week 16
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Regulatory T Cell (Treg) Marker Levels - PMBCs
Periodo de tiempo: At Baseline
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Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
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At Baseline
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Regulatory T Cell (Treg) Marker Levels - PMBCs
Periodo de tiempo: At Week 4
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Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
|
At Week 4
|
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Regulatory T Cell (Treg) Marker Levels - PMBCs
Periodo de tiempo: At Week 16
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Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
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At Week 16
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Regulatory T Cell (Treg) Marker Levels - TIL
Periodo de tiempo: At Baseline
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Amount of Regulatory T cell (Treg) markers present in TILs in treated patients.
|
At Baseline
|
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Regulatory T Cell (Treg) Marker Levels - TIL
Periodo de tiempo: At Week 4
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Amount of Regulatory T cell (Treg) markers present in TILs in treated patients.
|
At Week 4
|
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Activation and Maturation of Dendritic Cells - PBMC
Periodo de tiempo: At Baseline
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Measure of expression of activation and maturation of dendritic cells in PBMCs.
|
At Baseline
|
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Activation and Maturation of Dendritic Cells - PBMC
Periodo de tiempo: At Week 4
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Measure of expression of activation and maturation of dendritic cells in PBMCs.
|
At Week 4
|
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Activation and Maturation of Dendritic Cells - PBMC
Periodo de tiempo: At Week 16
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Measure of expression of activation and maturation of dendritic cells in PBMCs.
|
At Week 16
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Activation and Maturation of Dendritic Cells - TIL
Periodo de tiempo: At Baseline
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Measure of expression of activation and maturation of dendritic cells in tumor (TIL).
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At Baseline
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Activation and Maturation of Dendritic Cells - TIL
Periodo de tiempo: At Week 4
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Measure of expression of activation and maturation of dendritic cells in tumor (TIL).
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At Week 4
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Soluble LAG3 Levels - PBMC
Periodo de tiempo: At the time of disease progression - up to 4 years
|
Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in blood in patients that had previously demonstrated complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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At the time of disease progression - up to 4 years
|
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Soluble LAG3 Levels - TIL
Periodo de tiempo: At the time of disease progression - up to 4 years
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Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in tumor tissue in patients that had previously demonstrated complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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At the time of disease progression - up to 4 years
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Granzyme B Serum Levels
Periodo de tiempo: At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks
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Level of granzyme B (a serine protease secreted cells to mediate apoptosis in target cells) in serum.
|
At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks
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T Cell Count
Periodo de tiempo: At 4 weeks
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Number of T cells present in TIL or PBMC.
|
At 4 weeks
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T Cell Count
Periodo de tiempo: At 12 weeks
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Number of T cells present in TIL or PBMC.
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At 12 weeks
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T Cell Count
Periodo de tiempo: At the time of disease progression - up to 4 years
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Number of T cells present in TIL or PBMC.
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At the time of disease progression - up to 4 years
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Single Cell RNA Sequencing
Periodo de tiempo: 2 weeks
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The presence and quantity of RNA in in blood and tumor tissue.
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2 weeks
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Single Cell RNA Sequencing
Periodo de tiempo: At 4 weeks post Cycle 1
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The presence and quantity of RNA in in blood and tumor tissue.
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At 4 weeks post Cycle 1
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Single Cell RNA Sequencing
Periodo de tiempo: At week 16 (12 weeks post combination treatment (3 cycles)
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The presence and quantity of RNA in in blood and tumor tissue.
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At week 16 (12 weeks post combination treatment (3 cycles)
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Single Cell RNA Sequencing
Periodo de tiempo: At the time of disease progression - up to 4 years
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The presence and quantity of RNA in in blood and tumor tissue in patients that had previously demonstrated complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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At the time of disease progression - up to 4 years
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: John Kirkwood, MD, University of Pittsburgh
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Neoplasias por tipo histológico
- Enfermedades de la piel
- Tumores neuroectodérmicos
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Tumores neuroendocrinos
- Nevos y Melanomas
- Neoplasias De La Piel
- Enfermedades de la piel y del tejido conectivo
- Melanoma
- Aminoácidos, péptidos y proteínas
- Proteínas
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Nivolumab
- relatlimab
Otros números de identificación del estudio
- 18-071
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .