E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and metastatic gastrointestinal cancer |
Cáncer gastrointestinal avanzado y metastásico |
|
E.1.1.1 | Medical condition in easily understood language |
Gastrointestinal cancer |
Cáncer gastrointestinal |
|
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061534 |
E.1.2 | Term | Oesophageal squamous cell carcinoma |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030137 |
E.1.2 | Term | Oesophageal adenocarcinoma |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
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 | 21.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the antitumor activity of SAR444245 in combination with other anticancer therapies |
Determinar la actividad antitumoral de SAR444245 en combinación con otros tratamientos antineoplásicos |
|
E.2.2 | Secondary objectives of the trial |
- To assess the safety of SAR444245 when combined with other anticancer therapies - To assess other indicators of antitumor activity - To assess the pharmacokinetics of SAR444245 when given in combination with other anticancer therapies - To assess the immunogenicity of SAR444245 - Only for sub study 04 – Cohort D2: To assess active concentrations of cetuximab when given in combination with SAR444245 |
- Evaluar la seguridad de SAR444245 en combinación con otros tratamientos antineoplásicos. - Evaluar otros indicadores de la actividad antitumoral. - Evaluar la farmacocinética (FC) de SAR444245 en combinación con otros tratamientos antineoplásicos - Evaluar la inmunogenicidad de SAR444245. - Sólo para el subestudio 04 – Cohorte D2: Evaluar la concentración activa de cetuximab cuando se administra en combinación con SAR444245. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Sub-study01: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic esophageal squamous cell carcinoma Protocol number: ACT16902-S01, version 01 dated on 2021-08-30 - Sub-study02: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic gastric cancer or gastro-esophageal junction adenocarcinoma Protocol number: ACT16902-S02, version 01 dated on 2021-08-30 - Sub-study03: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic hepatocellular carcinoma Protocol number: ACT16902-S03, version 01 dated on 2021-08-30 - Sub-study04: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab or cetuximab for the treatment of participants with advanced and metastatic colorectal cancer Protocol number: ACT16902-S04, version 01 dated on 2021-08-30
For related objectives, refer to E.2.1 and E.2.2. |
- Subestudio 01: Estudio de fase 2 no aleatorizado, abierto, de múltiples cohortes, multicéntrico, para evaluar el beneficio clínico de SAR444245 (THOR-707) combinado con pembrolizumab para el tratamiento de participantes con carcinoma epidermoide esofágico avanzado y metastásico. Número de Protocolo SAR444245-ACT16902-S01, versión 01 de fecha 30-ago-2021
- Subestudio 02: Estudio de fase 2 no aleatorizado, abierto, de múltiples cohortes, multicéntrico, para evaluar el beneficio clínico de SAR444245 (THOR-707) combinado con pembrolizumab para el tratamiento de participantes con cáncer gástrico o adenocarcinoma de la unión gastroesofágica avanzado y metastásico. Número de Protocolo SAR444245-ACT16902-S02, versión 01 de fecha 30-ago-2021
- Subestudio 03: Estudio de fase 2 no aleatorizado, abierto, de múltiples cohortes, multicéntrico, para evaluar el beneficio clínico de SAR444245 (THOR-707) combinado con pembrolizumab para el tratamiento de participantes con carcinoma hepatocelular avanzado y metastásico. Número de Protocolo SAR444245-ACT16902-S03, versión 01 de fecha 30-ago-2021
- Subestudio 04: Estudio de fase 2 no aleatorizado, abierto, de múltiples cohortes, multicéntrico, para evaluar el beneficio clínico de SAR444245 (THOR-707) combinado con pembrolizumab o cetuximab para el tratamiento de participantes con cáncer colorrectal avanzado y metastásico. Número de Protocolo SAR444245-ACT16902-S04, versión 01 de fecha 30-ago-2021
Para objetivos relacionados, ver E.2.1 y E.2.2. |
|
E.3 | Principal inclusion criteria |
Participant must be ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent. Participants with: - Sub-study01: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic esophageal cancer of the squamous cell carcinoma subtype - Sub-study02: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 & 3 GEJ. - Sub-study03: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic HCC, or clinically by AASLD criteria in cirrhotic patients. - Sub-study04: Histologically or cytologically confirmed diagnosis of advanced unresectable or mCRC. Only patients with non-MSI-H disease are eligible. Participants (all sub-studies) must have at least one measurable lesion Mandatory baseline biopsy for the first 20 participants to enroll in sub-study01, sub-study02 and sub-study04. On-treatment biopsy for at least 20 participants in sub-study04. On-treatment biopsies are otherwise optional per Investigator’s discretion for the other cohorts.
Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees: - to use approved contraception method and submit to regular pregnancy testing prior to treatment and for at least 180 days after discontinuing study treatment - and to refrain from donating or cryopreserving eggs for 180 days after discontinuing study treatment.
Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment.
Capable of giving signed informed consent |
El participante debe tener ≥18 años (o la mayoría de edad legal del país si es >18 años) al momento de firmar el consentimiento informado.
Participantes con:
- Subestudio 01: Diagnóstico confirmado histológica o citológicamente del cáncer avanzado o metastásico de esófago del subtipo de carcinoma epidermoide - Subestudio 02: Diagnóstico confirmado histológicamente o citológicamente de CG o AGE tipo 2 y 3 según la clasificación Siewert avanzado o metastásico.
- Subestudio 03: Diagnóstico de CHC avanzado o metastásico confirmado histológicamente o citológicamente o clínicamente según los criterios de la AASLD en pacientes cirróticos (los pacientes sin cirrosis deben haber tenido confirmación histológica del diagnóstico).
- Subestudio 04: Diagnóstico confirmado histológicamente o citológicamente de cáncer colorrectal avanzado o metastásico. Sólo los pacientes con enfermedad sin inestabilidad microsatelital alta son aptos.
Los participantes (todos los subestudios) deben tener al menos una lesión medible. Biopsia obligatoria para los primeros 20 pacientes incluidos en el subestudio 01, subestudio 02 y subestudio 04. Biopsias durante el tratamiento para al menos 20 pacientes en el subestudio 04. De lo contrario, las biopsias durante el tratamiento son opcionales a discreción del investigador para las otras cohortes. Una mujer cumple los requisitos para participar si no está embarazada o amamantando, no es una mujer con capacidad de concebir o es una mujer con capacidad de concebir y acepta: - usar un método anticonceptivo aprobado y someterse a test de embarazo regulares antes del tratamiento y al menos hasta 180 días tras discontinuar el tratamiento del estudio - abstenerse de donar ni crioconservar óvulos (ovocitos) hasta 180 días tras discontinuar el tratamiento del estudio
Los participantes del sexo masculino pueden participar si están de acuerdo con abstenerse de donar o crioconservar semen y o bien abstenerse de tener relaciones heterosexuales o utilizar métodos anticonceptivos aprobados durante el período de tratamiento y durante al menos 210 días tras discontinuar el tratamiento del estudio.
Capaz de dar su consentimiento informado. |
|
E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 - Poor organ function - Active brain metastases or leptomeningeal disease. - History of allogenic or solid organ transplant. - Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery within 28 days prior to first IMP administration - Comorbidity requiring corticosteroid therapy - Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP - Severe or unstable cardiac condition within 6 months prior to starting study treatment - Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years - Participants with baseline SpO2 ≤92% (without oxygen therapy). - Participant has received prior IL2-based anticancer treatment. - Participants on sub-study02 cohort B1 and B2 or sub-study 04 – cohort D1 with prior treatment with an agent that blocks the PD-1/PD-L1 pathway. - Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted |
Se excluirá del estudio a los participantes que cumplan alguno de los siguientes criterios:
- Estado funcional según el Grupo Oncológico Cooperativo de la Costa Este (ECOG) ≥2. - Función orgánica deficiente - Metástasis cerebrales activas o metástasis leptomeníngeas - Antecedentes de trasplante de tejido alogénico/órgano sólido - Última administración de tratamiento antitumoral previo o cualquier tratamiento de investigación en un plazo de 28 días o menos de 5 veces la semivida, lo que sea más corto; cirugía mayor en un plazo de 28 días previos a la primera administración del MI - Comorbilidad que requiera tratamiento con corticoesteroides - Uso de antibióticos (excluidos los antibióticos tópicos) ≤ 14 días antes de la primera dosis del MI - Afección cardíaca grave o inestable en los 6 meses anteriores al inicio del tratamiento del estudio - Enfermedad autoinmunitaria activa, conocida o sospechada, que requirió tratamiento sistémico en los últimos 2 años - Participantes con una SpO2 inicial ≤92 % (sin oxigenoterapia). - El participante ha recibido tratamiento antineoplásico previo basado en IL-2 - Participantes de las cohortes B1 y B2 o subestudio 04- cohorte D1 con tratamiento previo con un agente que bloquee la vía de PD-1/PD-L1 - Haber recibido una vacuna de virus vivos en los 28 días previos al inicio del tratamiento programado. Se permiten las vacunas antigripales estacionales que no contengan virus vivos. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) |
Tasa de Respuesta Objetiva (TRO) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to the date of first documentation of progression, assessed approximatively up to 9 months after the first dose |
Desde el inicio hasta la fecha de primera progresión de la enfermedad documentada, evaluada aproximadamente hasta 9 meses después de la primera dosis |
|
E.5.2 | Secondary end point(s) |
1- Assessment of SAR444245 safety profile when combined with other anti-cancer therapies 2- Time to response 3- Duration of response 4- Clinical benefit rate 5- Progression-free survival 6- Concentrations of SAR444245 7- Incidence of anti-drug antibodies (ADAs) against SAR444245 8- Ctrough of infusion of cetuximab 9- Cend of infusion of cetuximab |
1- Evaluación del perfil de seguridad de SAR444245 cuando se administra encombinación con otras terapias antineoplásicas 2- Tiempo de respuesta 3- Duración de la respuesta 4- Tasa de beneficio clínico 5- Supervivencia libre de progresión 6- Concetración de SAR444245 7- Incidencia de anticuerpos antifármaco (AAF) contra SAR444245 8- C minima de la infusion de cetuximab 9- C final de la infusion de cetuximab |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1:SAE:from 1st IMP dose up to 90 days after the last dose of IMP AE/TEAE:from 1st IMP dose up to 30 days after the last dose of IMP 2to5:Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in 6:At Day1, 2, 3 of Cycle1 and Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21days), maximum is up to approximately 24 months 7:At Day 1 and 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle and 30 days after last IMP administration, maximum is up to approximately 24 months 8:Day1 of Cycle1-2-4-7-10 + every 5th cycle and 30 days after last IMP administration, maximum is up to approximately 24 months 9:Day1 of Cycle1-2-4-7-10 + every 5th cycle, maximum is up to approximately 24 months |
1: AAG: desde primera dosis del MI hasta 90 días después de última dosis del MI. AA/ AADT: desde primera dosis del MI hasta 30 días después de última dosis del MI 2 a 5: desde el inicio hasta fecha de primera progresión documentada, evaluada aprox hasta 18 meses después de inclusión del último paciente. 6: a Día 1, 2, 3 de Ciclo1 y Día 1 de ciclos 2-4-7-10 y cada 5º ciclo (cada ciclo son 21 días), hasta aprox un máx de 24 meses 7: a Día 1 y 15 de Ciclo1 y Día 1 de ciclos 2-4-7-10 y cada 5º ciclo y 30 días después de última administración del MI, hasta aprox un máx de 24 meses 8: Día 1 de Ciclos 1-2-4-7-10 y cada 5º ciclo y 30 días después de última administración del MI, hasta aprox un máximo de 24 meses 9: Día 1 de Ciclos 1-2-4-7-10 y cada 5º ciclo, hasta aprox un máximo de 24 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 | 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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | Information not present in EudraCT |
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.8.2.4 | Number of treatment arms in the trial | 7 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
China |
Korea, Republic of |
Russian Federation |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
|
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
|
LVLS |
La última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
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 | 6 |