E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer |
Cáncer de pulmón no microcítico en fase temprana (I [> 2 cm] a IIIA) |
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E.1.1.1 | Medical condition in easily understood language |
Early-stage Non-small Cell Lung Cancer |
Cáncer de pulmón no microcítico en fase temprana |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029517 |
E.1.2 | Term | Non-small cell lung cancer stage I |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029518 |
E.1.2 | Term | Non-small cell lung cancer stage II |
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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
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 |
Efficacy - Assess the antitumor activity of durvalumab alone and/or in combination with novel agents |
Eficacia - Evaluar la actividad antitumoral de durvalumab en monoterapia y/o en combinación con fármacos innovadores |
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E.2.2 | Secondary objectives of the trial |
Safety - Assess the feasibility of receiving the planned surgical resection - Assess the safety and tolerability of durvalumab alone and/or in combination with novel agents
Efficacy - Assess the antitumor activity of durvalumab alone and/or in combination with novel agents
Pharmacokinetics - To describe the PK of durvalumab alone and/or in combination with novel agents
Immunogenicity (a) To assess the immunogenicity of durvalumab alone or in combination with novel agents (b) To assess the immunogenicity of novel biologic agents in combination with durvalumab |
Seguridad - Evaluar la viabilidad de la realización de la resección quirúrgica programada - Evaluar la seguridad y tolerabilidad de durvalumab en monoterapia y/o en combinación con fármacos innovadores
Eficacia - Evaluar la actividad antitumoral de durvalumab en monoterapia y/o en combinación con fármacos innovadores
Farmacocinética - Describir la FC de durvalumab en monoterapia y/o en combinación con fármacos innovadores
Inmunogenia (a) Evaluar la inmunogenia de durvalumab en monoterapia o en combinación con fármacos innovadores (b) Evaluar la inmunogenia de agentes biológicos innovadores en combinación con durvalumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Cytologically and/or histologically-documented NSCLC (a) Stage I (> 2 cm) to IIIA (For subjects with N2 disease, only those with 1 single nodal station <= 3 cm are eligible) NSCLC (b) Amenable to complete surgical resection (c) Have not received any other therapy for this condition 2. Age >=18 years old 3. Predicted FEV1 >=≥ 50% 4. Predicted DLCO ≥ 50% 5. ECOG 0 or 1 6. Adequate organ function |
1. CPNM confirmado mediante histología o citología (a) CPNM en estadio de I (>2 cm) a IIIA (en pacientes con enfermedad N2, solo son aptos aquellos con 1 sola estación ganglionar <=3 cm) (b) Susceptible de resección quirúrgica completa (c) No haber recibido ningún otro tratamiento para la enfermedad
2. Edad >=18 años de edad 3. VEF1 previsto >=50 % 4. DLCO prevista >=50 % 5. ECOG 0 o 1 6. Funcionamiento adecuado de los órganos |
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E.4 | Principal exclusion criteria |
1. Subjects with small-cell lung cancer or mixed small-cell lung cancer 2. Subjects who require or may require pneumonectomy 3. Prior treatment with PD-L1, PD-L1, or CTLA-4 inhibitors 4. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. 5. Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: a. Subjects with vitiligo or alopecia b. Subjects with hypothyroidism on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Subjects without active disease in the last 5 years may be included but only after consultation with the study physician e. Subjects with celiac disease controlled by diet alone 6. Pregnant or breast-feeding female 7. Major surgical procedure within prior 30 days 8. History of active primary immunodeficiency 9. Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV 10. QTc interval (QTc) >= 470 ms 11. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent 12. Receipt of live attenuated vaccination within 30 days prior to study entry 13. History of another primary malignancy except for: a. Curative-treated malignancy with no known active disease > 2 years before enrollment on the study b. Curative-treated non-melanoma skin cancer and/or carcinoma in-situ |
1. Pacientes con cáncer de pulmón microcítico o cáncer de pulmón microcítico mixto 2. Pacientes que requieren o puedan requerir una neumonectomía 3. Tratamiento previo con PD-L1 o inhibidores de CTLA-4 4. Uso simultáneo o previo de inmunosupresores en los 14 días anteriores a la primera dosis de fármaco del estudio 5. Trastornos autoinmunitarios o inflamatorios documentados o activos. Se aplicarán las siguientes excepciones a este criterio: a. Pacientes con vitíligo o alopecia b. Pacientes con hipotiroidismo que reciban tratamiento de reposición hormonal c. Cualquier enfermedad cutánea crónica que no requiera tratamiento sistémico d. Los pacientes sin actividad de la enfermedad en los últimos 5 años pueden incluirse, pero solo después de consultar al médico del estudio e. Pacientes con enfermedad celíaca controlada solo con dieta
6. Mujeres embarazadas o en período de lactancia 7. Pacientes que se hayan sometido a cirugía mayor en los 30 días anteriores 8. Antecedentes de inmunodeficiencia primaria activa 9. Infección activa, incluida tuberculosis, hepatitis B, hepatitis C o VIH 10. Intervalo QTc (QTc) >=470 ms 11. Enfermedad intercurrente no controlada que limitaría el cumplimiento de los requisitos del estudio, que incrementaría sustancialmente el riesgo de AA provocados o que comprometería la capacidad del paciente para otorgar el consentimiento informado por escrito 12. Administración de una vacuna atenuada elaborada con microbios vivos en los 30 días anteriores a la inclusión en el estudio 13. Antecedentes de otra neoplasia maligna primaria, excepto: a. Neoplasia maligna tratada con tratamiento curativo sin enfermedad activa conocida >2 años antes de la inclusión en el estudio b. Cáncer de piel no melanocítico o carcinoma in situ tratado con tratamiento curativo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical activity - Major Pathological Response (MPR) rate |
Actividad clínica: - Tasa de respuesta anatomopatológica mayor (RAM) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MPR will be done in the resected specimen. Surgery is planned to take place within 14 days after the 4 weeks treatment period. |
Se investigará una respuesta anatomopatológica mayor en la muestra resecada. Se prevé que la cirugía se produzca en el plazo de 14 días tras el periodo de tratamiento de 4 semanas. |
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E.5.2 | Secondary end point(s) |
Safety - Feasibility, defined as having the planned surgical resection within Day 29 to Day 42 after Week 1, Day 1 - Presence of AEs, SAEs, laboratory abnormalities, and vital signs
Efficacy - Pathological Complete Response (pCR) rate
Pharmacokinetics - Concentration of durvalumab or novel agents in plasma or serum
Immunogenicity - ADA incidence of durvalumab or novel biologic agents |
Seguridad - Viabilidad que se define como la realización de la resección quirúrgica programada entre el día 29 y el día 42 después del día 1 de la semana 1 - Presencia de AA, AAG, anomalías de laboratorio y constantes vitales
Eficacia - Tasa de respuesta anatomopatológica completa (RAC)
Farmacocinética - Concentración de durvalumab o de agentes innovadores en suero o plasma
Inmunogenia - Incidencia de AAF contra durvalumab o agentes biológicos innovadores |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety - Feasibility - Surgery is planned to take place within 14 days after the 4 weeks treatment period. - AEs, SAEs, laboratory abnormalities, and vital signs - Up to 126 days after C1D1
Efficacy - pCR will be done in the resected specimen. Surgery is planned to take place within 14 days after the 4 weeks treatment period.
Pharmacokinetics and Immunogenicity - Up to 126 days after C1D1 |
Seguridad - Viabilidad: se prevé que la cirugía se produzca en el plazo de 14 días tras el periodo de tratamiento de 4 semanas. - AA, AAG, anomalías de laboratorio y constantes vitales: hasta 126 días después de D1C1
Eficacia - Se investigará una respuesta anatomopatológica completa en la muestra resecada. Se prevé que la cirugía se produzca en el plazo de 14 días tras el periodo de tratamiento de 4 semanas.
Farmacocinética e inmunogenia - Hasta 126 días después de D1C1 |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Inmunogenia |
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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) | 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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Estudio de plataforma |
Platform study |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Canada |
France |
Italy |
Portugal |
Spain |
Switzerland |
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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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment for the last subject in the study. This date will be 1 year after the final subject is entered into the study or when the sponsor stops the study, whichever occurs first. |
El fin del Estudio (“conclusión del estudio”) se define como la fecha de la última visita/evaluación especificada en el protocolo del último paciente del estudio. Esta fecha será 1 año después de la entrada en el estudio del último paciente o cuando el promotor detenga el estudio, lo que suceda primero. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |