| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-small Cell Lung Cancer |
| Cáncer de pulmón no microcítico |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-small Cell Lung Cancer |
| Cáncer de pulmón no microcítico |
|
| 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 | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 whether M7824 improves ORR compared with pembrolizumab in
first-line participants with advanced NSCLC with high PD-L1 tumor expression
To evaluate whether M7824 improves PFS compared with pembrolizumab in
first-line participants with advanced NSCLC with high PD-L1 tumor expression |
Evaluar si M7824 mejora la TRO en comparación con pembrolizumab en pacientes en primera línea con CPNM avanzado con una elevada expresión tumoral de PD-L1.
Evaluar si M7824 mejora la SSP en comparación con pembrolizumab en pacientes en primera línea con CPNM avanzado con una elevada expresión tumoral de PD-L1 |
|
| E.2.2 | Secondary objectives of the trial |
Safety
-To evaluate the safety and tolerability of M7824 compared with pembrolizumab
Efficacy
-To evaluate whether M7824 improves overall survival time compared with pembrolizumab
- ORR assessed by Investigators
- PFS assessed by Investigators
- DOR
PK
-To characterize PK profile of M7824
Immunogenicity
-To characterize the immunogenicity
of M7824 |
Seguridad
-Evaluar la seguridad y tolerabilidad de M7824 en comparación con pembrolizumab
Eficacia
-Evaluar si M7824 mejora el tiempo de supervivencia general en comparación con pembrolizumab
-TRO evaluada por los investigadores
-SSP evaluada por los investigadores |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. >= 18 years of age inclusive, at the time of signing the informed consent
2. histologically confirmed diagnosis of advanced NSCLC and:
a. Have not received prior systemic therapy treatment for their advanced/Stage IV
NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy,
and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy
was completed at least 6 months prior to the diagnosis of metastatic disease.
Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant
chemotherapy therapy to Grade ≤ 1. For radiation toxicity or prior major surgeries,
participants should have recovered from side effects and/or complications.
b. Have measurable disease based on RECIST 1.1
c. Have a life expectancy of at least 3 months
d. Availability of either tumor archival material (< 6 months old) or fresh biopsies
collected within 28 days (excluding bone biopsies) before the first dose is mandatory
to determine PD-L1 expression level prior to enrollment
e. PD-L1 high status is required
(other protocol defined criteria could apply) |
1.>= 18 años al tiempo de firma del consentimiento informado
2. Diagnóstico confirmado histológicamente de CPNM avanzado y:
a. No han recibido tratamiento de terapia sistémica previo para su etapa avanzada / IV
CPNM. Finalización del tratamiento con quimioterapia citotóxica, terapia biológica,
y / o la radiación como parte de la terapia neoadyuvante / adyuvante está permitida siempre que la terapia se completó al menos 6 meses antes del diagnóstico de enfermedad metastásica.
Confirmación de la resolución de los efectos tóxicos de neoadyuvante previo / adyuvante
terapia de quimioterapia de Grado ≤ 1. Para toxicidad por radiación o cirugías mayores previas,
los participantes deberían haberse recuperado de los efectos secundarios y / o complicaciones.
segundo.
b.Tener una enfermedad mensurable basada en RECIST 1.1
c. Tener una esperanza de vida de al menos 3 meses
d. Disponibilidad de material de archivo tumoral (<6 meses de edad) o biopsias frescas
recogidos dentro de los 28 días (excluidas las biopsias óseas) antes de que la primera dosis sea obligatoria para determinar el nivel de expresión de PD-L1 antes de la inscripción
mi.
e. El estado alto de PD-L1 es requerido
(se pueden aplicar otros criterios definidos por el protocolo) |
|
| E.4 | Principal exclusion criteria |
1. The participant’s tumor harbors an EGFR sensitizing (activating) mutation, ALK
translocation, ROS1 rearrangement, or BRAF V600E mutation, if targeted therapy is
locally approved
2. Has received major surgery within 4 weeks prior to the first dose of study intervention;
received thoracic RT of > 30 Gy within 6 months prior to the first dose of study
7. Known severe hypersensitivity reactions to mAB
8. Receipt of any organ transplantation
9. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required
oral or IV steroids
10. Significant acute or chronic infections
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with participation for the full
duration of the study, or is not in the best interest of the participant, in the opinion of the
treating Investigator
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways)
intervention.
13. Previous malignant disease
14. Has active CNS metastases causing clinical symptoms or metastases that require
therapeutic intervention and/or carcinomatosis meningitis
15. Active autoimmune disease that has required systemic treatment in past 1 year OR is
receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or
receiving any other form of immunosuppressive medication.
16. Is expected to require any other form of systemic or localized antineoplastic therapy
while on study (including maintenance therapy with another agent for NSCLC, RT,
and/or surgical resection)
(other protocol defined criteria could apply) |
1. El tumor del participante alberga una mutación sensibilizante (activadora) de EGFR, ALK
translocación, reordenamiento ROS1 o mutación BRAF V600E, si la terapia dirigida es
Aprobado localmente
2. Ha recibido una cirugía mayor dentro de las 4 semanas anteriores a la primera dosis de la intervención del estudio;recibió RT torácica de> 30 Gy en los 6 meses previos a la primera dosis del estudio
7. Reacciones de hipersensibilidad graves conocidas a mAB
8. Recibo de cualquier trasplante de órgano
9. Tiene enfermedad pulmonar intersticial (EPI) O ha tenido un historial de neumonitis que ha requerido esteroides orales o IV
10. Agudo agudo significativo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1) BOR according to RECIST 1.1
assessed by IRC
2) PFS according to RECIST 1.1
assessed by IRC |
1) MRG según RECIST 1.1 evaluada por el CRI
2)SSP según RECIST 1.1 evaluada por el CRI |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Time from randomization to planned final assessment for unconfirmed BOR, expected at
26 months.
2) Time from randomization to planned final assessment for PFS after 192 events expected
at 37 months. |
1) Tiempo desde la aleatorización hasta la evaluación final planificada para la MRG no confirmada, prevista a los 26.
2) Tiempo desde la aleatorización hasta la evaluación final planificada para la SSP después de 192 acontecimientos, prevista a los 37 meses. |
|
| E.5.2 | Secondary end point(s) |
1) Occurrence of TEAEs and treatment-related AEs according
to NCI-CTCAE v5.0
2) OS
3) BOR according to RECIST 1.1 assessed by Investigator
4) PFS according to RECIST 1.1 assessed by Investigator
5) DOR assessed from CR or PR according to RECIST 1.1 assessed by IRC until PD, death,
or last tumor assessment
6) PK profile of M7824 in terms of Ceoi
7) PK profile of M7824 in terms of
Ctrough
8) Immunogenicity as measured by ADA assays at Baseline and ontreatment |
1) Aparición de AAST y AA relacionados con el tratamiento conforme a CTCAE del NCI v 5.0
2) SG
3) MRG según RECIST 1.1 evaluada por el investigador
4) SSP según RECIST 1.1 evaluada por el investigador
5) DdR evaluada a partir de RC o RP según RECIST 1.1, evaluada por el CRI hasta la PE, la muerte o la última evaluación del tumor
6) Perfil FC de M7824 en términos de Cfdi
7)Perfil FC de M7824 en términos de Cvalle
8) La inmunogenicidad se determinará mediante análisis de AAF al inicio y durante el tratamiento. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Time from random. to the last 12-week safety follow-up visit, expected at 47 months.
2) From random. to assessment when 200 OS events occur, OS PA exp. at 49 months from first participant in the study
3) Time from random. to planned final assessment for unconfirmed BOR, exp. 26 months.
4) Time from random. to final assessm.PFS after 192 events at 37 months.
5) Time from CR or PR to planned assessment after 192 PFS events, expected at 37 months.
6,7) Predose samples at Weeks 1,3,5,7, then 6 weekly during treatment; postdose (within 30 min) samples at 6 weekly during treatment and up to study’s Safety Follow-up Visit at 28 days after last study intervention administ.
8) From random. up to study’s Safety Folup Visit, defined as 28 days after last study intervention administr. |
1) Tpo dsd la aleator hasta la última VSeg de la seguridad, 47m.
2) Tpo dsd la aleator hasta que se hayan producido 200 acontecimientos de SG; AP de SG, 49m desde la inclusión del 1 part.
3) Tpo dsd la aleator hasta la eva. final planificada para la MRG no confr, 26m
4) Tpo dsd la aleator hasta la evaluación final planificada para la SSP después de 192 acontecimientos, 37m
5) Tpo desde RC o RP hasta el criterio de valor plan dps de 192 acontecimientos de SSP, 37m
6,7 ) Muestras anteriores a la dosis en las semanas 1, 3, 5 y 7, y posteriormente cada 6sms durante el tto; muestras posteriores a la dosis (30 min) cada 6sem durante el tto y hasta la VSG de la seguridad al cabo de 28d dsd ultm adm
8) Tiempo desde la aleatorización hasta la VSG de la seguridad, 28d después de la utl adm |
|
| 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 | No |
| 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) | 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 | 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 | 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| 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 |
| Canada |
| European Union |
| Japan |
| United States |
|
| 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
|
| The end of the study is defined as the date when 67% of participants have had an OS event. |
| El final del estudio esta definido como la fecha en la que el 67% de pacientes han tenido un evento adverso |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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