| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced solid tumors |
| Tumores sólidos avanzados |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer of the cervix, Uterine (endometrial), Head and Neck, Bile duct, Esophagus, Breast (kind of breast cancer that does no have any receptor commonly found in breast cancer) and Liver Cancer |
| Cáncer de cuello uterino, útero (endometrial), cabeza y cuello, vías biliares, esófago, mama (sin ningún receptor de los que se encuentran comúnmente en el cáncer de mama) y cáncer de hígado |
|
| 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 |
|
| 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 |
1. To compare MK-7684A to pembrolizumab alone with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) in participants with cervical cancer whose tumors express programmed cell death 1 ligand 1 (PD-L1) [combined positive score (CPS) ≥1)] enrolled in Cohort A1.
2. To compare MK-7684A to pembrolizumab alone with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR in participants with cervical cancer whose tumors express PD-L1 (CPS ≥1) enrolled in Cohort A1.
3. To evaluate MK-7684A alone or in combination with other anticancer therapies with respect to ORR per RECIST 1.1 as assessed by the investigator in participants with selected solid tumors, excluding those with cervical cancer whose tumors express PD-L1 (CPS ≥1) enrolled in Cohort A1. |
1. Comparar MK-7684A con pembrolizumab en monoterapia en cuanto a la tasa de respuestas objetivas (TRO) conforme a los criterios RECIST 1.1, evaluada mediante una revisión central independiente y enmascarada (RCIE), en participantes con cáncer de cuello uterino cuyos tumores expresan PD-L1 (puntuación positiva combinada [PPC]≥1) incluidas en la cohorte A1.
2. Comparar MK-7684A con pembrolizumab en monoterapia en cuanto a la supervivencia sin progresión (SSP) conforme a los criterios RECIST 1.1, evaluada mediante una RCIE, en participantes con cáncer de cuello uterino cuyos tumores expresan PD-L1 (PPC≥1) incluidas en la cohorte A1.
3. Evaluar MK-7684A en monoterapia o en combinación con otros tratamientos antineoplásicos en cuanto a la TRO conforme a los criterios RECIST 1.1, evaluada por el investigador en participantes con tumores sólidos seleccionados, exceptuando aquellas con cáncer de cuello uterino cuyos tumores expresan PD-L1 (PPC≥1) incluidas en la cohorte A1. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate MK-7684A alone or with other anticancer therapies for overall survival (OS).
2. To evaluate MK-7684A alone or with other anticancer therapies for PFS per RECIST 1.1 as assessed by investigator in participants with selected solid tumors except those enrolled in Cohort A1.
3. To evaluate MK-7684A alone for duration of response (DOR) per RECIST 1.1 as assessed by BICR in participants enrolled in Cohort A1.
4. To evaluate MK-7684A alone or with other anticancer therapies for DOR per RECIST 1.1 as assessed by investigator in participants with selected solid tumors, except those enrolled in Cohort A1.
5. To evaluate change from baseline in health-related quality-of-life (HRQoL) using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life questionnaire core 30 (QLQ-C30) in participants enrolled in Cohort A1.
6. To evaluate the safety and tolerability of MK-7684A alone or with other anticancer therapies. |
1. Evaluar MK-7684A en monoterapia o combinación con otros ttos. antineoplásicos según supervivencia global (SG)
2. Evaluar MK-7684A en monoterapia o combinación con otros ttos. antineoplásicos según SSP conforme criterios RECIST 1.1, evaluada por investigador en participantes con tumores sólidos seleccionados, excepto cohorte A1
3. Evaluar MK-7684A en monoterapia según duración de respuesta (DR) conforme a criterios RECIST 1.1, evaluada mediante RCIE en cohorte A1
4. Evaluar MK-7684A en monoterapia o combinación con otros ttos. antineoplásicos según DR conforme criterios RECIST 1.1, evaluada por investigador en participantes con tumores sólidos seleccionados, excepto cohorte A1
5. Evaluar la variación respecto al valor basal de calidad de vida relacionada con la salud (CVRS) según cuestionario QLQ-C30 de EORTC en cohorte A1
6. Evaluar la seguridad y tolerabilidad de MK-7684A en monoterapia o combinación con otros ttos. antineoplásicos |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A participant will be eligible for inclusion in the study if the participant:
Has histologically- or cytologically-confirmed, advanced (locally recurrent unresectable or metastatic) solid tumor as follows:
1. Cohort A: squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has progressed on standard of care chemotherapy with or without radiation but must not have been treated with prior anti-PD-1/PD L1 therapy. Chemotherapy given with radiation therapy will not be considered a first-line therapy.
- Cohort A1: participants whose tumors are PD-L1 positive (CPS ≥1) as determined by the central laboratory
- Cohort A2: participants whose tumors are PD-L1 negative (CPS <1) as determined by the central laboratory
2. Cohort B: endometrial cancer that has progressed after 1 prior systemic, platinum-based chemotherapy regimen for endometrial cancer but must not have been treated with prior anti-PD-1/ PD L1 therapy. Participants may have received up to 2 lines of platinum-based chemotherapy if 1 was given in the neoadjuvant or adjuvant treatment setting.
- Cohort B1: participants with endometrial cancer whose tumors are dMMR as determined by the central laboratory
- Cohort B2: participants with endometrial cancer whose tumors are pMMR as determined by the central laboratory
3. Cohort C: HNSCC that is considered incurable by local therapies and whose tumors express PD-L1 (CPS ≥1) as determined by the local laboratory using the PD-L1 IHC 22C3 pharmDx assay.
Note: participants may not have a primary tumor site of nasopharynx (any histology)
4. Cohort D: unresectable biliary adenocarcinoma (gallbladder or biliary tree [intrahepatic or extrahepatic] cholangiocarcinoma) that has progressed after 1 prior systemic therapy but must not have been treated with prior anti-PD-1/ PD L1 therapy.
5. Cohort E: adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the GEJ (defined as adenocarcinomas of the lower esophagus with the center located within 1 cm to 5 cm above the anatomic GEJ) that is unresectable and has not been previously treated with systemic therapy, including anti-PD-1/ PD L1 therapy, administered in the recurrent or metastatic setting.
6. Cohort F: locally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines, that is either locally recurrent unresectable not previously treated with chemotherapy and that cannot be treated with curative intent or metastatic that has not been previously treated with chemotherapy.
7. Cohort G: HCC with any of the following criteria:
Radiologically, histologically, or cytologically-confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors that has not been previously treated with systemic therapy, including anti-PD-1/PD L1 therapy. Radiographic confirmation of the diagnosis must be confirmed by the study site.
8. Has measurable disease per RECIST 1.1 as assessed by the BICR (Cohort A1 only) or local site investigator/radiology (all other cohorts). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Note: For Cohort A1, BICR must confirm the presence of radiologically measurable disease based on RECIST 1.1 for the participant to be eligible for the study.
9. Can provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival FFPE tumor tissue block or slides for determination of biomarker status (eg, PD L1, MMR, ER, PgR, BRCA, and HER2/neu). A newly obtained biopsy is preferred, but not required if archival tissue is available for analysis.
10. Has an ECOG performance status of either 0 or 1, as assessed within 7 days before starting study intervention.
11. Has a predicted life expectancy of at least 3 months.
12. Has adequately controlled BP with or without antihypertensive medications, defined as bp ≤150/90 mm hg at screening and no change in antihypertensive medications within 1 week before allocation.
Note: this criterion only applies to participants who will receive lenvatinib in either Cohort B2 or Cohort G. |
En el estudio podrá participar todo candidato que cumpla los criterios siguientes:
Presencia de un tumor sólido avanzado (localmente recurrente irresecable o metastásico) confirmado histológica o citológicamente, tal como sigue:
1. Cohorte A: carcinoma epidermoide, carcinoma adenoepidermoide o adenocarcinoma de cuello uterino que haya progresado con la quimioterapia habitual, con o sin radioterapia, pero no debe haber sido tratado previamente con anti-PD-1/PD-L1. La quimioterapia administrada con radioterapia no se considerará un tratamiento de primera línea.
- Cohorte A1: participantes cuyos tumores sean positivos para PD-L1 (PPC≥1) según lo determinado por el laboratorio central
- Cohorte A2: participantes cuyos tumores sean negativos para PD-L1 (PPC<1) según lo determinado por el laboratorio central
2. Cohorte B: cáncer de endometrio que ha progresado después de 1 pauta previa de quimioterapia sistémica a base de platino para el cáncer de endometrio, pero no debe haber sido tratado previamente con anti-PD-1/PD-L1. Las participantes pueden haber recibido hasta 2 líneas de quimioterapia a base de platino si una se administró en el contexto del tratamiento neoadyuvante o adyuvante
- Cohorte B1: participantes con cáncer de endometrio cuyos tumores son dMMR, según lo determinado por el laboratorio central
- Cohorte B2: participantes con cáncer de endometrio cuyos tumores son pMMR según lo determinado por el laboratorio central
3. Cohorte C: CECC que se considera incurable con tratamientos locales y cuyos tumores expresan PD-L1 (PPC ≥1), según lo determinado por el laboratorio local mediante la prueba de IHQ de PD-L1 22C3 pharmDx
Nota: Los participantes no pueden presentar un tumor primario de nasofaringe (de cualquier histología)
4.C ohorte D: adenocarcinoma biliar irresecable (colangiocarcinoma de la vesícula biliar o del árbol biliar [intrahepático o extrahepático]) que haya progresado después de un tratamiento sistémico previo, pero no debe haber sido tratado previamente con anti-PD-1/PD-L1
5.C ohorte E: adenocarcinoma o carcinoma epidermoide del esófago o adenocarcinoma de la UGE de tipo 1 de Siewert avanzado/metastásico (definidos como adenocarcinomas de la parte baja del esófago con el centro localizado entre 1 y 5 cm por encima de la UGE anatómica) que es irresecable y no ha sido tratado previamente con terapia sistémica, incluido el tratamiento anti-PD-1/PD-L1, administrado en el contexto recurrente o metastásico
6. Cohorte F: CMTN confirmado localmente, según lo definido en las guías más recientes de la ASCO/CAP, que sea localmente recurrente irresecable no tratado previamente con quimioterapia y que no pueda tratarse con intención curativa o metastásico no tratado previamente con quimioterapia
7.C ohorte G: CHC con cualquiera de los siguientes criterios:
Diagnóstico de CHC confirmado radiológica, histológica o citológicamente, excluidos los tumores CHC fibrolamelar, sarcomatoide o colangio-CHC mixto que no hayan sido tratados previamente con terapia sistémica, incluido el tratamiento anti-PD-1/PD-L1. La confirmación radiológica del diagnóstico deberá ser confirmada por el centro del estudio
8. Presencia de enfermedad mensurable conforme a los criterios RECIST 1.1, evaluada mediante una RCIE (solo cohorte A1) o según la evaluación del investigador o radiólogo del centro (todas las demás cohortes). Las lesiones situadas en una zona previamente irradiada se considerarán mensurables siempre que se haya constatado progresión en dichas lesiones
Nota: En el caso de la cohorte A1, la RCIE deberá confirmar la presencia de enfermedad mensurable radiológicamente conforme a los criterios RECIST 1.1 para que el participante sea apto para el estudio
9. Se puede proporcionar una biopsia con aguja gruesa o por escisión reciente de una lesión tumoral o bien un bloque o preparaciones en portaobjetos de tejido tumoral fijado en formol e incluido en parafina (FFIP) de archivo para determinar la expresión de biomarcadores (p. ej., PD-L1, MMR, RE, RPg, BRCA y HER2/neu). Es preferible una biopsia reciente, pero no será obligatoria si se dispone de tejido de archivo para el análisis
10. Estado funcional del ECOG de 0 o 1 determinado en los 7 días previos al comienzo de la intervención del estudio
11. Esperanza de vida prevista de al menos 3 meses
12. Presión arterial debidamente controlada, con o sin antihipertensivos, definida como una PA ≤150/90 mm Hg en la selección y sin modificaciones de los antihipertensivos en la semana previa a la asignación.
Nota: Este criterio se aplica únicamente a los participantes que recibirán lenvatinib en la cohorte B2 o la cohorte G |
|
| E.4 | Principal exclusion criteria |
The participant must be excluded from the study if the participant:
1. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in-situ cervical cancer, or other in-situ cancers
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-TIGIT agent
3. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation
Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. Participants with Grade ≤2 alopecia are eligible
4. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
Note: Participants who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent
5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging (Note: The repeat imaging should be performed during study screening.), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study intervention
Note: Participants with known untreated, asymptomatic brain metastases (ie, no neurological symptoms, no requirement for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate but will require regular imaging of the brain as a site of disease
6. Known severe hypersensitivity (≥Grade 3) to MK-7684A, pembrolizumab (Cohort A1 only), lenvatinib (Cohort B2 and Cohort G only), paclitaxel (Cohort F only), or 5-FU and cisplatin (Cohort E only) and/or any of their excipients.
7. Has an active autoimmune disease requiring systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
8. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
For participants who will receive lenvatinib in either Cohort B2 or Cohort G:
9. Has received previous treatment with lenvatinib
Note: Prior therapy with other kinase inhibitors that target VEGF are not exclusionary
10. Has had major surgery within 3 weeks before first dose of study interventions
Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
11. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
12. Has urine protein ≥1 g/24 hours
Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria
13. Has a LVEF below the institutional (or local laboratory) normal range, as determined by MUGA or ECHO
14. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
NOTE: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy
15. Has prolongation of QTcF interval to >480 ms
NOTE: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility
16. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted
17. Has serious nonhealing wound, ulcer, or bone fracture
18. Has GI malabsorption or any other condition that might affect the absorption of lenvatinib
19. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study intervention
20. Has a history of arterial thromboembolism within 12 months of start of study intervention
For participants who will receive paclitaxel in Cohort F:
21. Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization |
1.Antecedentes de segunda neoplasia maligna, a menos que haya completado un tto. potencialmente curativo sin signos de neoplasia maligna durante 3 años.
Nota: El requisito de tiempo no es aplicable a participantes sometidos a resección definitiva satisfactoria de .carcinoma basocelular de piel, carcinoma espinocelular de piel, cáncer de cuello uterino in situ u otros cánceres in situ.
2.Haber recibido tto. con fármaco anti-PD-1, anti-PD-L1, anti-PD-L2 o anti-TIGIT.
3.Haber recibido tto. antineoplásico sistémico previo, incluidos fármacos experimentales, en las 4 semanas previas a aleatorización.
Nota: Haberse recuperado a grado≤1 o situación inicial de todos los AAs debidos a ttos. previos. Podrán participar pacientes con neuropatía grado≤2; AAs grado≤2 relacionados con sistema endocrino que requieran tto. o reposición hormonal; alopecia grado≤2.
4.Participación activa o pasada en estudio de fármaco en investigación o uso de producto sanitario en investigación en 4 las semanas previas a 1a dosis del estudio.
Nota: Podrán participar pacientes que hayan comenzado fase de seguimiento de estudio de investigación si han transcurrido al menos 4 semanas desde última dosis del anterior fármaco en investigación.
5.Metástasis activas en SNC y/o meningitis carcinomatosa conocidas. Podrán participar pacientes con metástasis cerebrales tratadas previamente, siempre que se encuentren radiológicamente estables (sin signos de progresión) durante al menos 4 semanas según estudios de imagen repetidos (Los estudios de imagen deberán repetirse durante la selección), estén clínicamente estables y no tengan necesidad de tto. con esteroides durante al menos 14 días antes de 1a dosis del estudio.
Nota: Participantes con metástasis cerebrales asintomáticas no tratadas conocidas (sin síntomas neurológicos, sin necesidad de corticoides, sin edema circundante [o solo mínimo] y sin lesiones>1,5cm) podrán participar, pero deberán someterse a estudios de imagen periódicos del cerebro como foco de enfermedad.
6.Hipersensibilidad grave conocida (grado≥3) a MK-7684A, pembrolizumab (cohorte A1), lenvatinib (cohortes B2 y G), paclitaxel (cohorte F) o 5-FU y cisplatino (cohorte E) o a cualquiera de sus excipientes.
7.Presencia de enfermedad autoinmunitaria activa que haya precisado tto. sistémico (modificadores de la enfermedad, corticosteroides o inmunodepresores) en los 2 últimos años. El tto. de reposición (p. ej., tiroxina, insulina o corticoides en dosis fisiológicas por insuficiencia suprarrenal o hipofisaria) no se considera una forma de tto. sistémico y se permitirá su uso.
8.Antecedentes de neumonitis (no infecciosa)/neumopatía intersticial que precisó esteroides o presencia de neumonitis/neumopatía intersticial.
Participantes que reciban lenvatinib en cohortes B2 o G:
9. Ha recibido tto. previo con lenvatinib.
Nota: Tto. previo con otros inhibidores de cinasas dirigidos contra VEGF no es motivo de exclusión.
10.Antecedentes de intervención de cirugía mayor en las 3 semanas previas a 1a dosis del estudio.
Nota: Debe hacerse valoración clínica de la adecuada curación de la herida tras intervención de cirugía mayor, independientemente del tiempo transcurrido, a efectos de elegibilidad.
11.Presencia de fístula gastrointestinal o no gastrointestinal grado≥3.
12.Proteinuria≥1g/24horas.
Nota: Participantes con proteinuria≥2+ (≥100 mg/dl) en análisis de orina con tira reactiva se someterán a recogida de orina de 24hs para evaluación cuantitativa de proteinuria.
13.FEVI por debajo del intervalo normal del centro, determinada mediante MUGA o ecocardiograma.
14.Signos radiológicos de atrapamiento o invasión de vaso sanguíneo importante o de cavitación intratumoral.
NOTA: El grado de proximidad a vasos sanguíneos importantes debe tenerse en cuenta por posible riesgo de hemorragia profusa asociada a reducción o necrosis del tumor después de tto. con lenvatinib.
15.Prolongación intervalo QTcF>480ms.
NOTA: Si prolongación QTcF>480ms en presencia de marcapasos, contactar con promotor para determinar elegibilidad.
16.Presencia de enfermedad cardiovascular significativa en los 12 meses previos a 1a dosis del estudio, como insuficiencia cardíaca congestiva clase III o IV NYHA, angina inestable, infarto de miocardio, accidente cerebrovascular o arritmia cardíaca asociada a inestabilidad hemodinámica.
Nota: Se permite presencia de arritmia médicamente controlada.
17.Herida o úlcera no curada o fractura ósea no consolidada grave.
18.Presencia de malabsorción gastrointestinal u otra afección que pueda afectar a la absorción de lenvatinib.
19.Hemoptisis activa en las 3 semanas previas a 1a dosis del fármaco del estudio.
20.Antecedentes de tromboembolia arterial en los 12 meses previos al inicio de intervención del estudio
Participantes que reciban paclitaxel en cohorte F:
21.Antecedentes de insuficiencia cardíaca congestiva de clase II-IV o infarto de miocardio en los 6 meses previos a aleatorización. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR).
2. Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR.
3. ORR per RECIST 1.1 as Assessed by Investigator. |
1. Tasa de Respuestas Objetivas (TRO) conforme a los criterios RECIST 1.1, según evaluación de una Revisión Central Independiente y Enmascarada (RCIE).
2. Supervivencia sin progresión (SSP) conforme a los criterios RECIST 1.1, según evaluación de una RCIE.
3. TRO conforme a los criterios RECIST 1.1, según evaluación del investigador. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 36 months.
2. Up to approximately 36 months.
3. Up to approximately 36 months. |
1. Hasta aproximadamente 36 meses.
2. Hasta aproximadamente 36 meses.
3.Hasta aproximadamente 36 meses. |
|
| E.5.2 | Secondary end point(s) |
1. Overall Survival (OS).
2. PFS per RECIST 1.1 as Assessed by Investigator.
3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR.
4. DOR per RECIST 1.1 as Assessed by Investigator.
5. Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30] Items 29 and 30).
6. Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5).
7. Number of Participants Who Experienced One or More Adverse Events (AEs).
8. Number of Participants Who Discontinued Study Intervention Due to an AE. |
1. Supervivencia global (SG).
2. SSP conforme a los criterios RECIST 1.1, según evaluación del investigador.
3. Duración de la Respuesta (DR) conforme a los criterios RECIST 1.1, según evaluación de una RCIE.
4. DR conforme a los criterios RECIST 1.1, según evaluación del investigador.
5. Variación con respecto al valor basal en puntuación del estado general de salud/Calidad de Vida (ítems 29 y 30 del cuestionario de calidad de vida de 30 ítems [EORTC QLQ-C30]; European Organisation for Research and Treatment of Cancer (Organización Europea para la Investigación y el Tratamiento del Cáncer)).
6. Variación con respecto al valor basal en Puntuación de la función física (ítems 1 a 5 del QLQ-C30 de la EORTC).
7. Número de participantes que experimentaron uno o más Acontecimientos Adversos (AA).
8. Número de participantes que interrumpieron el tratamiento del estudio debido a un AA. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 36 months.
2. Up to approximately 36 months.
3. Up to approximately 36 months.
4. Up to approximately 36 months.
5. Baseline and up to approximately 36 months.
6. Baseline and up to approximately 36 months.
7. Up to approximately 36 months.
8. Up to approximately 35 months. |
1. Hasta aproximadamente 36 meses
2. Hasta aproximadamente 36 meses
3. Hasta aproximadamente 36 meses
4. Hasta aproximadamente 36 meses
5. Basal y hasta aproximadamente 36 meses
6. Basal y hasta aproximadamente 36 meses
7. Hasta aproximadamente 36 meses
8. Hasta aproximadamente 35 meses |
|
| 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 | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Exploratory biomarker analysis |
|
| 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 |
|
| 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 | 6 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| 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 |
| Chile |
| Colombia |
| Israel |
| Japan |
| Korea, Republic of |
| Taiwan |
| Turkey |
| United States |
| France |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Spain |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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