E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Esophageal or Gastric Cancer |
Esofágico metastásico o Cáncer Gástrico |
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E.1.1.1 | Medical condition in easily understood language |
Esophageal or Gastric Cancer |
Esofágico o Cáncer Gástrico |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 overall survival (OS) of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with high PD-L1 expression. • To compare OS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in all randomized participants. |
•Evaluar la supervivencia global (SG) con domvanalimab + zimberelimab + quimioterapia en comparación con nivolumab + quimioterapia, en los participantes con expresión alta de PD-L1. •Evaluar la SG de domvanalimab + zimberelimab + quimioterapia en comparación con nivolumab + quimioterapia, en todos los participantes aleatorizados. |
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E.2.2 | Secondary objectives of the trial |
•To compare PFS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in participants with high PD-L1 expression •To compare PFS of domvanalimab + zimberelimab + chemotherapy versus nivolumab + chemotherapy in all randomized participants •To assess additional measures of clinical activity in participants with high PD-L1 expression and in all randomized participants •To assess the safety and tolerability of domvanalimab + zimberelimab + chemotherapy in all randomized participants |
•Evaluar la supervivencia sin progresión (SSP) con domvanalimab + zimberelimab + quimioterapia en comparación con nivolumab + quimioterapia, en los participantes con expresión alta de PD-L1. •Evaluar la SSP de domvanalimab + zimberelimab + quimioterapia en comparación con nivolumab + quimioterapia, en todos los participantes aleatorizados. •Evaluar indicadores adicionales de la actividad clínica en los participantes con expresión alta de PD-L1 y en todos los participantes aleatorizados. •Evaluar la seguridad y tolerabilidad de domvanalimab + zimberelimab + quimioterapia en todos los participantes aleatorizados. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma. •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1. •At least one measurable target lesion per RECIST v1.1. •Adequate organ and marrow function •Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing |
•Participantes con diagnóstico confirmado histológicamente de adenocarcinoma gástrico, eso-fágico o de la UGE irresecable o metastásico localmente avanzado. •Estado funcional del Grupo Oncológico Cooperativo de la Costa Este (ECOG) de los EE. UU. de 0-1. •Mínimo una lesión indicadora medible conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST v1.1). •Funcionamiento adecuado de los órganos y la médula ósea. •Capacidad para proporcionar una muestra tumoral de archivo representativa del cáncer en Investigación y adecuada para el análisis central del ligando 1 de la proteína de muerte celular programada (PD-L1). |
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E.4 | Principal exclusion criteria |
•Underlying medical or psychiatric conditions that, in the investigator’s or sponsor’s opinion, will make the administration of study-specified therapy hazardous •Known HER-2-positive tumor. •Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. •Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma. •Use of any live vaccines within 28 days prior to randomization. |
•Afecciones médicas o trastornos psiquiátricos subyacentes que, en opinión del investigador o del promotor, hagan que la administración del tratamiento específico del estudio sea peligrosa. •Constancia de tumor positivo para HER2. •Constancia de metástasis en el sistema nervioso central (SNC o cerebro) sintomáticas, sin tratar o en progresión activa. •Recepción de tratamiento sistémico previo para el adenocarcinoma gástrico, esofágico o de la UGE irresecable o metastásico localmente avanzado. •Uso de vacunas con microbios vivos en los 28 días previos a la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• OS is defined as the length of time from date of randomization until the date of death from any cause |
•La SG se define como el intervalo de tiempo transcurrido desde la fecha de la aleatorización hasta la fecha de la muerte por cualquier causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to the Protocol |
Por favor, consulte el protocolo. |
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E.5.2 | Secondary end point(s) |
• PFS is defined as the time from date of randomization until disease progression or death from any cause, whichever comes first, as measured per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the investigator. • Objective response rate (ORR) is defined as the proportion of participants who have achieved confirmed complete response (CR) or confirmed partial response (PR) to study therapy as assessed by the investigator according to RECIST 1.1. • Duration of response (DOR) is measured from the time of first response (CR or PR as measured by RECIST 1.1) as assessed by the investigator, until the date of first documented disease progression or death, whichever comes first. • The incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and any clinically meaningful trends in safety parameters. |
•La SSP se define como el tiempo transcurrido desde la fecha de la aleatorización hasta la progresión de la enfermedad o la muerte por cualquier causa, lo que suceda antes, de acuerdo con la evaluación del investigador conforme a los Criterios de Evaluación de la Respuesta en Tumores Sólidos, versión 1.1 (Response Evaluation Criteria in Solid Tumors, RECIST v1.1). •La tasa de respuesta objetiva (TRO) se define como la proporción de participantes que logran una respuesta completa (RC) confirmada o una respuesta parcial (RP) confirmada al tratamiento del estudio, de acuerdo con la evaluación del investigador conforme a los criterios RECIST v1.1. •La duración de la respuesta (DR) se mide desde el momento de la primera respuesta (RC o RP conforme a los criterios RECIST v1.1) de acuerdo con la evaluación del investigador, hasta la fecha de la primera progresión de la enfermedad documentada o la muerte, lo que suceda antes. •Incidencia e intensidad de los acontecimientos adversos (AA) y los acontecimientos adversos graves (AAG) y cualquier tendencia clínicamente significativa en los parámetros de la seguridad. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please, refer to the Protocol |
Por favor, consulte el protocolo. |
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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) | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 91 |
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 |
Brazil |
Canada |
Chile |
China |
Colombia |
Guatemala |
Hong Kong |
Israel |
Japan |
Malaysia |
Mexico |
Peru |
Philippines |
Thailand |
United States |
European Union |
Georgia |
Turkey |
United Kingdom |
Serbia |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |