E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Solid Tumors |
Tumores sólidos avanzados |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Solid Tumors |
Tumores sólidos avanzados |
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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 | 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 determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of BMS-986178 administered alone and in combination with nivolumab or ipilimumab in subjects with advanced malignant tumors. |
Determinar la seguridad, tolerabilidad, toxicidades limitantes de la dosis (TLD) y dosis máxima tolerada (DMT)/dosis recomendada para fase 2 (DRF2) de BMS-986178 administrado en monoterapia y en combinación con nivolumab o ipilimumab en sujetos con tumores malignos avanzados |
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E.2.2 | Secondary objectives of the trial |
To investigate the preliminary anti-tumor activity of BMS-986178 administered alone and in combination with nivolumab or ipilimumab in subjects with advanced malignant tumors To characterize the pharmacokinetics (PK) of BMS-986178 administered alone and in combination with nivolumab or ipilimumab To characterize the immunogenicity of BMS-986178 administered alone and in combination with nivolumab or ipilimumab and the immunogenicity of nivolumab or ipilimumab administered with BMS-986178 |
Investigar la actividad antitumoral preliminar de BMS-986178 administrado en monoterapia y en combinación con nivolumab o ipilimumab en sujetos con tumores malignos avanzados Caracterizar la farmacocinética (FC) de BMS-986178 administrado en monoterapia y en combinación con nivolumab o ipilimumab Caracterizar la inmunogenicidad de BMS-986178 administrado en monoterapia y en combinación con nivolumab o ipilimumab y la inmunogenicidad de nivolumab o ipilimumab administrado con BMS-986178 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must have at least 1 standard treatment regimen in the advanced, recurrent or metastatic setting • ECOG (Eastern Cooperative Oncology Group) 0-1 • Men and women 18 years old or older • At least one measurable lesion at baseline by CT (computed tomography) or MRI (magnetic resonance imaging) as per RECIST (Response Evaluation Criteria In Solid Tumors) v1.1 |
• Pacientes con al menos 1 régimen estándar de tratamiento en el tumor avanzado, recurrente o metastásica • ECOG (Eastern Cooperative Oncology Group) 0-1 • Hombres y mujeres de 18 años o más • Al menos una lesión medible al inicio del estudio por TAC (tomografía axial computarizada) o MRI (imágenes por resonancia magnética) de acuerdo con los criterios RECIST (Criterios de evaluación de respuesta en tumores sólidos) v1.1 |
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E.4 | Principal exclusion criteria |
• Known central nervous system metastases or central nervous system as the only source of disease • Concomitant malignancies • Active known or suspected autoimmune disease • Uncontrolled or significant cardiovascular disease • Major surgery less than 4 weeks before the start of the study |
• Metástasis conocida en el sistema nervioso central o sistema nervioso central como la única fuente de la enfermedad • Neoplasias concomitantes • Enfermedad autoinmune activa conocida o sospechada • Enfermedad cardiovascular significativa o no controlada • Cirugía mayor previa realizada con menos de 4 semanas antes de iniciar el estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AE's (adverse events) and SAE's (serious adverse events), AE's leading to discontinuation, deaths and clinical laboratory test abnormalities |
Incidencia de acontecimientos adversos (AA) y acontecimientos adversos graves (AAG), AA que provocan la discontinuación, muertes y anomalías en las pruebas clínicas de laboratorio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 4 years |
Durante 4 años |
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E.5.2 | Secondary end point(s) |
• Cmax (maximum observed serum concentration) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • Tmax (time of maximum observed concentration) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • AUC(0-t) (area under the concentration-time curve from time zero to the time) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • AUC(TAU) (area under the concentration-time curve in 1 dosing interval) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • Ctau (the observed concentration at the end of a dosing interval) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • CLT (total body clearance) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • Css-avg [average concentration over a dosing interval (AUC(TAU)/tau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • AI [ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC (TAU), Cmax and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • T-HALFeff [effective elimination half-life to explain degree of accumulation for a specific exposure measure (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • Ctrough [trough observed plasma concentrations (this includes pre-dose concentrations (C0) and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits • Immunoassay of anti-nivolumab antibody in combination with anti-BMS-986178 antibody • Immunoassay of anti-ipilimumab antibody in combination with anti-BMS-986178 antibody • Objective Response Rate (ORR) • Progression Free Survival Rate (PFSR) • Immunoassay of anti-BMS-986178 antibody alone |
• Cmax (concentración máxima en suero observada) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • Tmáx (tiempo de concentración máxima observada) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • AUC (0-t) (área bajo la curva de concentración-tiempo desde el tiempo cero al tiempo) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • AUC (TAU) (área bajo la curva de concentración-tiempo en el intervalo de dosificación 1) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • Ctau (la concentración observada al final de un intervalo de dosificación) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • CLT (aclaramiento corporal total) de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • Ceq‑prom [concentración media en un intervalo de dosis (AUC (TAU) / tau)] de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • AI [relación de una medida de la exposición en estado estacionario y después de la primera dosis (medida de la exposición incluye AUC (TAU), Cmax y Ctau)] de BMS-986178 en momonterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • T-MEDIAef [semivida de eliminación eficaz para explicar grado de acumulación de una medida específica de exposición (medida de la exposición incluye AUC (TAU), Cmax y Ctau)] de BMS-986178 en monoterapia y en combinación con nivolumab o ipilimumab, si se dispone de datos • Cvalle [concentraciones mínimas plasmáticas (esto incluye las concentraciones pre-dosis (C0) y Ctau)] de BMS-986178 solo y en combinación con nivolumab o ipilimumab, si se dispone de datos • Inmunoensayo de anticuerpo anti-nivolumab en combinación con anticuerpo anti-BMS-986178 • Inmunoensayo de anticuerpo anti-ipilimumab en combinación con anticuerpo anti-BMS-986178 • Tasa de respuesta objetiva (TRO) • Tasa de supervivencia libre de progresión (TSLP) • Inmunoensayo de anticuerpos anti-BMS-986178 solo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Cmax; Tmax; AUC(0-t); AUC(TAU); Ctau; CLT; Css-avg; AI; T-HALFeff; Ctrough; Immunoassay of anti-nivolumab antibody in combination with anti-BMS-986178 antibody; Immunoassay of anti-ipilimumab antibody in combination with anti-BMS-986178 antibody : Approximately 100 days after the final study drug administration (end of treatment) • ORR; PFSR: Approximately 2 years • Immunoassay of anti-BMS-986178 antibody alone: Approximately 100 days after 6 months of treatment |
• Cmax; Tmax; AUC(0-t); AUC(TAU); Ctau; CLT; Ceq-prom; índice de acumulación (IA); semivida de eliminación efectiva (T-MEDIAef); Cvalle; Inmunoensayo de anticuerpo anti-nivolumab en combinación con anticuerpo anti-BMS-986178; Inmunoensayo de anticuerpo anti-ipilimumab en combinación con anticuerpo anti-BMS-986178: aproximadamente 100 días después de la administración del medicamento en estudio final (final del tratamiento) • TRO; TSLP: Aproximadamente 2 años • Inmunoensayo de anticuerpo anti-BMS-986178 solo: aproximadamente 100 días después de 6 meses de tratamiento |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity: The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to BMS-986178 or nivolumab or ipilimumab. |
Inmunogenicidad: el objetivo secundario de la inmunogenicidad se evaluará por la frecuencia de AAF positivos frente a BMS-986178 o nivolumab o ipilimumab. |
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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 | Yes |
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 | No |
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 | 3 |
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 | 2 |
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 |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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LPLV |
Última vistita 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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |