E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer (NSCLC) |
Cáncer de pulmón no microcítico (CPNM) |
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E.1.1.1 | Medical condition in easily understood language |
NSCLC is the most common type of lung cancer that originally arises from the lungs and could spread to areas near the lungs or distantly to other organs. |
El CPNM es el tipo de cáncer de pulmón más común que surge originalmente de los pulmones y puede extenderse a áreas cercanas a los pulmones o de forma distante a otros órganos. |
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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 | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the progression-free survival (PFS) and overall survival (OS). |
Evaluar la eficacia de tiragolumab más atezolizumab en comparación con placebo más atezolizumab sobre la base de supervivencia sin progresión (SSP) y supervivencia global (SG). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the confirmed overall response rate (ORR), duration of response (DOR), PFS rate at 6 months and 12 months, OS rate at 12 months and 24 months, time to sustained deterioration and global health status • To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with placebo plus atezolizumab • To characterize pharmacokinetics of tiragolumab and atezolizumab • To evaluate the immune response to tiragolumab plus atezolizumab. |
• Evaluar la eficacia de tiragolumab más atezolizumab en comparación con placebo más atezolizumab sobre la base de la tasa de respuesta global (TRG) confirmada , la duración de la respuesta (DR), la tasa de SSP a los 6 meses y 12 meses, la tasa de SG a los 12 y 24 meses meses, tiempo de deterioro mantenido y estado de salud general • Evaluar la seguridad y la tolerabilidad del tiragolumab más atezolizumab en comparación con placebo más atezolizumab • Caracterizar la farmacocinética de tiragolumab y atezolizumab. • Evaluar la respuesta inmune al tiragolumab más atezolizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Histologically or cytologically documented locally advanced or recurrent NSCLC - No prior systemic treatment for metastatic NSCLC - Tumor PD-L1 expression as determined by PD-L1 IHC assay of archival tumor tissue - Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) - Adequate hematologic and end-organ function. |
- Edad> = 18 años - Estado de desempeño ECOG de 0 o 1 - CPNM localmente avanzado o recurrente documentado histológica o citológicamente - Sin tratamiento sistémico previo para el CPNM metastásico - Expresión tumoral PD-L1 determinada por el ensayo PD-L1 IHC de tejido tumoral de archivo - Enfermedad medible según los criterios de evaluación de respuesta en tumores sólidos, versión 1.1 (RECIST v1.1) - Adecuada función hematológica y del órgano terminal. |
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E.4 | Principal exclusion criteria |
- Known to have a mutation in the EGFR gene or an ALK fusion oncogene - Symptomatic, untreated, or actively progressing central nervous system metastases - Active or history of autoimmune disease or immune deficiency - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis - Significant cardiovascular disease - History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death - Severe infection within 4 weeks prior to initiation of study treatment - Current treatment with anti-viral therapy for HBV or HCV - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Prior treatment with CD137 agonists or immune checkpoint blockade therapies - Treatment with systemic immunostimulatory agents or anticipation of need for systemic immunosuppressive medication during study treatment prior to initiation of study treatment. |
- Se sabe que tiene una mutación en el gen EGFR o un oncogén de fusión ALK - Metástasis sintomáticas, no tratadas o que progresan activamente en el sistema nervioso central - Enfermedad activa o antecedentes de enfermedad autoinmune o inmunodeficiencia - Antecedentes de fibrosis pulmonar idiopática, neumonía organizada, neumonitis inducida por fármacos o neumonitis idiopática, o evidencia de neumonitis activa. - Enfermedad cardiovascular significativa - Antecedentes de malignidad que no sea CPNM dentro de los 5 años previos a la detección, con la excepción de malignidades con un riesgo insignificante de metástasis o muerte - Infección grave dentro de las 4 semanas previas al inicio del tratamiento del estudio. - Tratamiento actual con terapia antiviral para el VHB o VHC - Tratamiento con terapia de investigación dentro de los 28 días anteriores al inicio del tratamiento del estudio. - Tratamiento previo con agonistas de CD137 o terapias de bloqueo del punto de control inmunitario - Tratamiento con agentes inmunoestimuladores sistémicos o anticipación de la necesidad de medicación inmunosupresora sistémica durante el tratamiento del estudio antes del inicio del tratamiento del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. PFS as determined by the investigator according to RECIST v1.1 2. OS. |
1. SSP determinada por el investigador de acuerdo a RECIST v1.1 2. SG |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 59 months |
1-2. Hasta un maximo de 59 meses |
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E.5.2 | Secondary end point(s) |
1. Confirmed ORR as determined by the investigator according to RECIST v1.1 2. DOR as determined by the investigator according to RECIST v1.1 3. PFS rate at 6 months and 12 months as determined by the investigator according to RECIST v1.1 4. OS rate at 12 months and 24 months 5. Time to sustained deterioration in patient-reported physical functioning and global health status, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 6. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 7. Minimum serum concentration (Cmin) and Maximum serum concentrate (Cmax) of tiragolumab 8. Cmin and Cmax of atezolizumab 9. Prevalence of ADAs to tiragolumab and atezolizumab at baseline and during the study. |
1. TRG confirmada según lo determinado por el investigador de acuerdo con RECIST v1.1 2. DR según lo determinado por el investigador de acuerdo con RECIST v1.1 3. Tasa de SSP a los 6 y 12 meses según lo determine el investigador de acuerdo con RECIST v1.1 4. Tasa de SG a los 12 y 24 meses 5. Tiempo hasta el deterioro mantenido en el funcionamiento físico informado por el paciente y el estado de salud global, medido por el Cuestionario de calidad de vida del cáncer de la Organización Europea para la Investigación y el Tratamiento del Cáncer 6. Incidencia y gravedad de los eventos adversos, cuya gravedad se determina de acuerdo con los Criterios de terminología común del Instituto Nacional del Cáncer para eventos adversos, Versión 5.0 7. Concentración sérica mínima (Cmin) y concentrado sérica máxima (Cmax) de tiragolumab 8. Cmin y Cmax de atezolizumab 9. Prevalencia de ADA a tiragolumab y atezolizumab al inicio del estudio y durante el estudio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Up to 59 months |
1-9. Hasta un máximo de 59 meses |
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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 | 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 |
immune response |
respuesta inmune |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Austria |
Brazil |
China |
Denmark |
France |
Germany |
Greece |
Hungary |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Peru |
Poland |
Russian Federation |
Serbia |
Spain |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
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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 | |
E.8.9.1 | In the Member State concerned months | 59 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 59 |