E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Colorectal cancer (CRC), pancreatic cancer or non-small cell lung cancer (NSCLC), and other indications dependent on emerging data |
Cáncer colorrectal (CCR), cáncer pancreático y cáncer de pulmón no microcítico (CPNM), además de otras indicaciones basadas en datos que vayan apareciendo |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Pancreatic Cancer, Colorectal Cancer or Non-Small Cell Lung Cancer |
Cáncer pancreático avanzado, cáncer colorrectal o Cáncer colorrectal |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
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 |
Evaluate the safety and tolerability of AMG 820 administered in combination with pembrolizumab in subjects with select advanced solid tumors
Evaluate the objective response rate (ORR) of AMG 820 and pembrolizumab combination as per irRECIST in subjects with select advanced solid tumors |
-Evaluar la seguridad y la tolerabilidad de AMG 820 administrado en combinación con pembrolizumab en sujetos con tumores sólidos avanzados seleccionados. -Evaluar la tasa de respuesta objetiva (TRO) de la combinación de AMG 820 y pembrolizumab según los criterios irRECIST en sujetos con tumores sólidos avanzados seleccionados |
|
E.2.2 | Secondary objectives of the trial |
Evaluate the anti-tumor activity of AMG 820 and pembrolizumab combination in select advanced solid tumors by assessing - ORR per RECIST1.1 - time to response (TTR), duration of response (DOR), and time to progression (TTP) - progression free survival (PFS) and overall survival (OS) at 6 and 12 months
Characterize the pharmacokinetics (PK) of AMG 820 after intravenous (IV) infusion administration of AMG 820 in combination with pembrolizumab
Evaluate the relationship between the immune infiltrate status in pre-study tumor biopsies vs. clinical response |
Evaluar la actividad antitumoral de la combinación de AMG 820 y pembrolizumab en tumores sólidos avanzados seleccionados mediante la evaluación de: - la TRO según los criterios RECIST1.1; - el tiempo hasta la respuesta (THR), la duración de la respuesta (DR), y el tiempo hasta la progresión (THP); - la supervivencia libre de progresión (SLP) y la supervivencia global (SG) a los 6 y los 12 meses. Describir la farmacocinética (PK) de AMG 820 después de la administración de una perfusión intravenosa (IV) de AMG 820 en combinación con pembrolizumab. Evaluar la relación entre el estado del infiltrado inmune en biopsias del tumor previas al estudio frente a la respuesta clínica |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment. - Measurable disease per RECIST 1.1 guidelines. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 - Adequate hematologic, renal, and hepatic function determined by laboratory blood and urine tests. - Availability of recent tumor tissue with 3 months prior to enrollment, when feasible. |
- CCR, cáncer pancreático o CPNM avanzados patológicamente documentados y con un diagnóstico definitivo, que son refractarios al tratamiento estándar, o sujetos que han mostrado intolerancia o han rechazado el tratamiento estándar. -El sujeto debe presentar una enfermedad medible radiográfica y/o clínicamente según los criterios RECIST 1.1 (Eisenhauer et al., 2009). - Estado funcional ECOG de 0-1. - Función orgánica adecuada determinada antes de la inclusión, definida como: Hemtológica, renal y hepática determinada por análisis de sangre y orina. - A nivel basal, y siempre que sea posible, se requiere tener disponible una muestra de tejido tumoral reciente (de los 3 meses previos al día 1 y sin administración de tratamiento sistémico después de la biopsia) y evaluable para biomarcadores. - Para criterios de inclusión adicionales ver protocolo. |
|
E.4 | Principal exclusion criteria |
- Has known active central nervous system metastases - History of other malignancy with the past 2 years with some exceptions - Evidence of active non-infectious pneumonitis/interstitial lung disease - Evidence of other active autoimmune disease or significant immunosuppression that has required prolonged systemic treatment in past 2 years. - Prior chemotherapy, radiotherapy, biological cancer therapy or major surgery within 28 days prior to enrollment - Currently participating or has participated in a study (treatment period only) of an investigational agent or used an investigational device within 28 days of enrollment - Received live vaccine within 28 days prior to enrollment - Adverse event due to cancer therapy administered more than 28 days prior to enrollment that has not recovered to CTCAE grade 1 or better. - Positive for human immunodeficiency virus (HIV), Hepatitis B or C - Women planning to become pregnant or who are lactating/breastfeeding while on study through 4 months after receiving the last dose of study drug. - Active infection within 2 weeks prior to first dose of study treatment |
- El sujeto presenta metástasis activas conocidas en el sistema nervioso central (SNC). -Antecedentes de otros tumores malignos en los últimos 2 años, con algunas excepciones. -Evidencia de secuelas activas o radiológicas de neumonitis no infecciosa/enfermedad pulmonar intersticial. -Antecedentes o evidencia indicativa de otras enfermedades autoinmunes activas que hayan requerido tratamiento sistémico prolongado en los 2 últimos años. - Quimioterapia, radioterapia, terapia biológica para el cáncer o cirugía mayor previas en los 28 días anteriores a la inclusión. -Estar participando actualmente o haber participado en un estudio (período de tratamiento solamente) de un fármaco en investigación, o haber utilizado un dispositivo en investigación durante los 28 días previos a la inclusión. -Haber recibido vacunas con microorganismos vivos durante los 28 días previos a la inclusión. - Acontecimiento adverso debido a un tratamiento anticanceroso administrado más de 28 días antes de la inclusión que no se ha recuperado hasta un grado 1 o mejor de CTCAE. - Resultado positivo para el virus de la inmunodeficiencia humana (VIH), Hepatitis B y C. - Mujeres en período de lactancia o que planean dar el pecho durante el estudio y durante los 4 meses posteriores a recibir la última dosis del fármaco en estudio. -Infección activa dentro de las 2 semanas anteriores a la primera dosis del tratamiento del estudio - Para criterios de exclusion adicionales ver protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Dose limiting toxicities (DLT), treatment-emergent adverse events, treatment-related adverse events and clinically significant changes in vital signs, physical examinations, and clinical laboratory tests
- Objective response rate (ORR) per irRECIST in subjects treated at the recommended combination dose |
- Toxicidades limitantes de la dosis (TLD), acontecimientos adversos que aparecen durante el tratamiento, acontecimientos adversos relacionados con el tratamiento y cambios clínicamente significativos en las constantes vitales, las exploraciones físicas y las pruebas analíticas clínicas. - La TRO según los criterios irRECIST en sujetos tratados a la dosis de combinación recomendada. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At 6 months: once the target enrollment is complete and each subject has been treated for at least 6 months or responded or withdrawn from the study, the analysis of the primary endpoints will occur. 2. At 12 months: once the target enrollment is complete and each subject has been treated for at least 12 months or has been followed up for PFS and OS for 12 months or withdrawn from the study, the analysis of primary and secondary endpoints (safety endpoints, ORR, PFS and OS at 6 and 12 months) will occur
Final Analysis - after all subjects have ended the study |
1.A los 6 meses: el análisis de las variables principales se llevará a cabo una vez se haya completado la inclusión objetivo y cada sujeto haya sido tratado durante un mínimo de 6 meses o haya respondido o se haya retirado del estudio. 2.A los 12 meses: el análisis de las variables principales y secundarias (variables de seguridad, TRO, SLP y SG a los 6 y a los 12 meses) se llevará a cabo una vez se haya completado la inclusión objetivo y cada sujeto haya sido tratado durante un mínimo de 12 meses, o haya sido sometido a seguimiento para la SLP y la SG durante 12 meses, o se haya retirado del estudio Análisis final : Se ha planificado realizar un análisis final cuando todos los sujetos de la parte 1 y la parte 2 hayan finalizado el estudio |
|
E.5.2 | Secondary end point(s) |
- OR per RECIST 1.1; TTR, DOR and TTP; OS and PFS at 6 and 12 months - PK parameters for AMG 820 including, but not limited to, maximum observed concentration (Cmax) and minimum observed concentration (Cmin). In addition, area under the concentration-time curve (AUC) and, if feasible, half-life (t1/2) for AMG 820. - CD4, CD8 & CD68 cells number in fresh pre-treatment biopsies |
- Respuesta objetiva (RO) según los criterios RECIST 1.1; THR, DR y THP; SG y SLP a los 6 y a los 12 meses. - Parámetros PK para AMG 820 como la concentración máxima observada (Cmáx) y la concentración mínima observada (Cmín), entre otros. Asimismo, el área bajo la curva (AUC) de la concentración en función del tiempo y, si es posible, la semivida (t1/2) para AMG 820. - Los números de células CD4, CD8 y CD68 en biopsias recientes previas al tratamiento. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 6 months: once the target enrollment is complete and each subject has been treated for at least 6 months or responded or withdrawn from the study, the analysis of the primary endpoints will occur. 2. At 12 months: once the target enrollment is complete and each subject has been treated for at least 12 months or has been followed up for PFS and OS for 12 months or withdrawn from the study, the analysis of primary and secondary endpoints (safety endpoints, ORR, PFS and OS at 6 and 12 months) will occur
Final Analysis - after all subjects have ended the study |
1.A los 6 meses: el análisis de las variables principales se llevará a cabo una vez se haya completado la inclusión objetivo y cada sujeto haya sido tratado durante un mínimo de 6 meses o haya respondido o se haya retirado del estudio. 2.A los 12 meses: el análisis de las variables principales y secundarias (variables de seguridad, TRO, SLP y SG a los 6 y a los 12 meses) se llevará a cabo una vez se haya completado la inclusión objetivo y cada sujeto haya sido tratado durante un mínimo de 12 meses, o haya sido sometido a seguimiento para la SLP y la SG durante 12 meses, o se haya retirado del estudio Análisis final : Se ha planificado realizar un análisis final cuando todos los sujetos de la parte 1 y la parte 2 hayan finalizado el estudio |
|
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
United States |
|
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
|
Primary Completion: is anticipated to occur when all Study Part 1 and 2 subjects have been enrolled and treated for at least 12 months, been followed up for PFS and OS at 12 months or discontinued from the study.
End of Trial: LSLV |
Finalización principal: se prevé que tenga lugar cuando todos los sujetos de las partes 1 y 2 del estudio hayan sido incluidos y tratados durante un mínimo de 12 meses, hayan sido objeto de seguimiento de la SLP y la SG a los 12 meses o hayan interrumpido el estudio. Fin del estudio: último paciente, última visita |
|
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 | 3 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 3 |