E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors (squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), cutaneous melanoma, triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), urothelial carcinoma, gastric, esophageal, cervical, and colorectal cancer (CRC)). |
Tumores sólidos avanzados (carcinoma de células escamosas de cabeza y cuello (CCECyC), cáncer de pulmón no microcítico (CPNM), melanoma cutáneo, cáncer de mama triple negativo (CMTN), carcinoma de células renales (CCR), carcinoma urotelial, cáncer gástrico, cáncer de esófago, cáncer cervical y cáncer colorrectal (CRC)). |
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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 | 21.1 |
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 characterize the safety, tolerability, and Dose-Limiting Toxicities (DLTs) and to determine the Maximum Tolerated Dose (MTD)/ Recommended Phase 2 Dose (RP2D) of BMS-986288 administered as monotherapy and in combination with nivolumab in participants with select advanced solid tumors |
Caracterizar la seguridad, la tolerabilidad y las toxicidades limitadas por la dosis (TLD) y determinar la dosis máxima tolerada (DMT) /dosis recomendada de fase 2(DRF2) de BMS-986288 administrado en monoterapia y en combinación con nivolumab en participantes con tumores sólidos avanzados seleccionados |
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E.2.2 | Secondary objectives of the trial |
- To characterize the Pharmacokinetic (PK) of BMS-986288 when administered alone and in combination with nivolumab - To assess the preliminary efficacy of BMS-986288 alone and in combination with nivolumab in advanced solid tumors using RECIST v1.1 - To measure T-regulatory cells (Tregs), and assess Treg change over time and in association with response |
-Caracterizar la farmacocinética (FC) de BMS-986288 administrado en monoterapia y en combinación con nivolumab -Evaluar la eficacia preliminar de BMS-986288 en monoterapia y en combinación con nivolumab en tumores sólidos avanzados usando los criterios RECIST v1.1 -Medir los linfocitos T reguladores (Treg) y evaluar el cambio de Treg a lo largo del tiempo y en asociación con la respuesta |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologic or cytologic confirmation of select solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease and have at least 1 lesion accessible for biopsy - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to select solid tumor histologies
Other protocol defined inclusion criteria apply. |
- Confirmación histológica o citológica de un tumor sólido seleccionado que es avanzado (metastásico, recurrente y / o irresecable) con enfermedad medible y tener al menos una lesión accesible para biopsia - Estado funcional (ECOG) de 0 o 1 - Los participantes deben haber recibido y luego progresado, recaído o haber sido intolerantes a, al menos 1 régimen de tratamiento estándar en el estadio avanzado o metastásico según la histología del tumor sólido seleccionado
Otros criterios de inclusión definidos por el protocolo. |
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E.4 | Principal exclusion criteria |
- Participants with active, known or suspected autoimmune disease - Participants with other active malignancy requiring concurrent intervention - Participants with primary CNS malignancies or tumors with CNS metastasis as the only site of disease, will be excluded
Other protocol defined exclusion criteria apply. |
- Participantes con Enfermedad autoinmune active conocida o sospechada - Participantes con otras malignidades activas que requieren una intervención concurrente - Se excluyen los participantes con tumores malignos primarios con metástasis en el SNC como único lugar de enfermedad
Otros criterios de exclusión definidos por el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs meeting protocol-defined Dose Limiting Toxicities (DLT) Criteria, AEs leading to discontinuation, death and laboratory abnormalities |
1. Incidencia de AA, AAG, AA que cumplan los criterios de TLD definidos en el protocolo, que conduzcan a la suspensión, muerte y anomalías de laboratorio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 2 years |
1. Hasta 2 años |
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E.5.2 | Secondary end point(s) |
1. Maximum Observed Concentration (Cmax) of BMS-986288 2. Time of Maximum Observed Concentration (Tmax) of BMS-986288 3. Area Under the Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) of BMS-986288 4. Area Under the Concentration-Time Curve in one Dosing Interval AUC(TAU) of BMS-986288 5. Observed Concentration at the end of a Dosing Interval (Ctau) of BMS-986288 6. Trough Observed Concentrations (Ctrough) of BMS-986288 7. Total Body Clearance (CLT) of BMS-986288 8. Average Concentration Over a Dosing Interval at Steady State (Cavgss) of BMS-986288 9. Accumulation Index (AI) of BMS-986288 10. Terminal Half-Life (T-HALF) of BMS-986288 11. Incidence of Anti-Drug Antibodies (ADAs) to BMS-986288 12. Objective Response Rate (ORR) of Participants 13. Duration of Response (DOR) of Participants 14. Progression-Free Survival (PFS) of Participants 15. Time to Response (TTR) of Participants 16 Percentage of change from baseline in T-regulatory cells (Tregs) |
1- Concentración máxima observada (Cmax) de BMS-986288 2. Tempo de la concentración máxima observada (Tmax) de BMS-986288 3. Área bajo la concentración-Tiempo de la curva desde el tiempo cero hasta el tiempo de la última concentración cuantificable AUC(0-T) de BMS-986288 4. Área bajo la concentración -Tiempo de la curva en un intervalo de dosificación AUC(TAU) de BMS-986288 5. Concentración observada al final del intervalo de dosificación (Ctau) de BMS-986288 6. Concentraciones mínimas observadas (Ctrough) de BMS-986288 7. Aclaramiento corporal total (CLT) de BMS-986288 8. Concentración media sobre un intervalo de dosis en el estado estable (Cavgss) de BMS-986288 9. Índice de acumulación (IA) de BMS-986288 10. Vida media terminal (T-HALF) de BMS-986288 11. Incidencia de anticuerpos anti medicamento (ADAs) para BMS-986288 12. Tasa de respuesta objetiva (TRO) de los participantes 13. Duración de la respuesta (DOR) de los participantes 14. Supervivencia libre de progresión (SLP) de los participantes 15. Tiempo hasta la respuesta (TTR) de los participantes 16. Porcentaje del cambio desde el estado basal en los linfocitos T reguladores (Tregs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 2 years 2. Up to 2 years 3. Up to 2 years 4. Up to 2 years 5. Up to 2 years 6. Up to 2 years 7. Up to 4 months 8. Up to 4 months 9. Up to 4 months 10. Up to 4 months 11. Up to 2 years 12. Up to 4 years 13. Up to 4 years 14. Up to 4 years 15. Up to 4 years 16. Up to 2 years |
1. Hasta 2 años 2. Hasta 2 años 3. Hasta 2 años 4. Hasta 2 años 5. Hasta 2 años 6. Hasta 2 años 7. Hasta 4 meses 8 Hasta 4 meses 9. Hasta 4 meses 10 Hasta 4 meses 11. Hasta 2 años 12. Hasta 4 años 13. Hasta 4 años 14. Hasta 4 años 15. Hasta 4 años 16. Hasta 2 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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Different dose regimens of BMS-986288 alone and in combination with nivolumab. |
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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 | 11 |
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 |
Argentina |
Canada |
Italy |
Spain |
United States |
France |
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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
|
The end of the study for the trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities (see Protocol Section 2) for the last participant. |
El final del ensayo se define como la última visita o procedimiento programado que se muestra en el Programa de actividades (ver sección 2 del Protocolo) para el 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 7 |