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 |
|
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 |
The primary objective is to determine the safety, tolerability, dose-limiting toxicities (DLTs), and MTD/MAD/alternate dose of BMS-986156 administered alone and in combination with nivolumab in subjects with advanced solid tumors. |
El objetivo principal es determinar la seguridad, tolerabilidad, toxicidades limitantes de la dosis (TLD) y DMT/DMA/dosis alterna de BMS-986156 administrado en monoterapia y en combinación con nivolumab en sujetos con tumores sólidos avanzados. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate the preliminary anti-tumor activity of BMS-986156 administered alone and in combination with nivolumab in subjects with advanced solid tumors - To characterize the PK of BMS-986156 administered alone and in combination with nivolumab - To characterize the immunogenicity of BMS-986156 administered alone and in combination with nivolumab, and the immunogenicity of nivolumab administered with BMS-986156. |
- Investigar la actividad antitumoral preliminar de BMS-986156 administrado en monoterapia y en combinación con nivolumab en sujetos con tumores sólidos avanzados. - Caracterizar la FC de BMS-986156 administrado en monoterapia y en combinación con nivolumab. - Caracterizar la inmunogenicidad de BMS-986156 administrado en monoterapia y en combinación con nivolumab y la inmunogenicidad de nivolumab administrado con BMS-986156. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For Dose Escalation: - Subjects with any previously treated advanced (metastatic or refractory) solid tumor
For Cohort Expansion: - Subjects must have a previously treated advanced solid tumor to be eligible - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Willing and able to provide pre-treatment and on-treatment fresh tumor biopsy - Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men |
Para la escalada de dosis: - Sujetos con cualquier tipo de tumor sólido avanzado (metastásico o refractario) que haya sido tratado previamente.
Para la expansión de las cohortes: - Los sujetos deben tener un tumor sólido avanzado previamente tratado. - Estado funcional ECOG (Eastern Cooperative Oncology Group) de 0 a 1. - Dispuesto y capaz de proporcionar biopsias del tumor fresco antes y durante el tratamiento. - Las mujeres fértiles y los hombres deben usar un método anticonceptivo durante el tratamiento, las mujeres durante 23 semanas después del tratamiento y los hombres durante 31 semanas después del tratamiento. |
|
E.4 | Principal exclusion criteria |
- Known central nervous system metastases or central nervous system as the only source of disease - Other concomitant malignancies (with some exceptions per protocol) - Active, known or suspected autoimmune disease - Uncontrolled or significant cardiovascular disease - History of chronic hepatitis - History of active hepatitis (B or C) - Impaired liver or bone marrow function - Major surgery less than 1 month before start of the study |
- Metástasis conocidas del sistema nervioso central o enfermedad que tenga su único origen en el sistema nervioso central. - Otras enfermedades malignas concomitantes (con algunas excepciones por protocolo). - Enfermedad autoinmune activa, conocida o sospechada. - Enfermedad cardiovascular no controlada o significativa. - Historial de hepatitis crónica. - Historial de hepatitis activa (B o C). - Deterioro de la función hepática o de la médula ósea. - Cirugía mayor previa realizada con menos de 1 mes antes de iniciar el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The assessment of safety will be based on the incidence of AEs, SAEs, adverse events leading to discontinuation, and deaths. In addition clinical laboratory test abnormalities will be examined |
La evaluación de la seguridad se basará en la incidencia de acontecimientos adversos (AA), acontecimientos adversos graves (AAG), acontecimientos adversos que conduzcan a la suspensión y muertes. Además se examinárán anomalías en las pruebas de laboratorio clínico. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Non-serious AEs/SAEs will be collected starting with the first dose of study medication and through 100 days after discontinuation of dosing |
Se recogerán los acontecimientos adversos, tanto graves como no graves, desde la primera dosis de la medicación en estudio hasta 100 días después de la interrupción del tratamiento. |
|
E.5.2 | Secondary end point(s) |
1/ ORR, duration of response, and progression free survival rate (PFSR) 2/ Selected BMS-986156 parameters, such as Cmax, Tmax, AUC-(TAU), AUC (0-T) will be assessed, if feasible, from concentration-time data 3/ Frequency of positivex ADA to BMS-986156 and or nivolumab |
1/ TRO, duración de la respuesta y tasa de supervivencia libre de progresión (TSLP). 2/ Se evaluarán parámetros seleccionados de BMS-986156 como Cmax, Tmax, AUC-(TAU), AUC (0-T), si es factible, a partir de datos de concentración-tiempo. 3/ Incidencia de AAF específicos frente a BMS-986156 y/o nivolumab. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ Every 8 weeks during treatment, response and survival follow-up periods 2/ During Cycle 1 and Cycle 3 3/ During Cycle 1, Cycle 2 and Cycle 3 |
1/ Cada 8 semanas durante el período de tratamiento y los períodos de seguimiento de la respuesta y de la supervivencia. 2/ Durante el ciclo 1 y el ciclo 3. 3/ Durante el ciclo 1, el ciclo 2 y el ciclo 3. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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 | No |
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 | 4 |
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 | 19 |
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 |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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
|
LVLS |
Última visita del último sujeto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 10 |