E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Solid Tumors, per protocol GCT1044-01 |
tumores sólidos malignos, por protocolo GCT1044-01 |
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E.1.1.1 | Medical condition in easily understood language |
Solid Tumor |
tumores sólidos |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Dose Escalation Part: • Determine recommended phase 2 dose (RP2D) • Establish safety profile of GEN1044
Dose Expansion Part: • Evaluate anti-tumor activity |
Parte de aumento gradual de dosis: • Determinar la dosis recomendada fase 2 DRF2 •Establecer el perfil de seguridad de GEN1044
Parte de expansión de la dosis: •Evaluar la actividad antitumoral |
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E.2.2 | Secondary objectives of the trial |
Dose Escalation Part: • Establish PK profile • Evaluate immunogenicity of GEN1044 • Evaluate anti-tumor activity based on response assessment criteria (RECIST v1.1)
Dose Expansion Part: • Evaluate anti-tumor activity based on response assessment criteria (RECIST v1.1) • Evaluate efficacy • Further describe the safety profile of GEN1044 • Further describe the PK profile • Further describe the immunogenicity of GEN1044 |
Parte de aumento gradual de dosis: • Establecer el perfil de farmacocinética (FC) • Evaluar la inmunogenicidad de GEN1044 • Evaluar la actividad antitumoral según los criterios de evaluación de la respuesta (RECIST v1.1)
Parte de expansión de la dosis: •Evaluar la actividad antitumoral según los criterios de evaluación de la respuesta (RECIST v1.1) •Evaluar la eficacia •Describir adicionalmente el perfil de seguridad de GEN1044 •Describir adicionalmente el perfil de farmacocinética (FC) •Describir adicionalmente la inmunogenicidad de GEN1044 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject with locally advanced or metastatic solid tumor(s) (excluding subjects with primary central nervous system [CNS] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy. 2. Must be ≥18 years of age. 3. Subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the trial and is willing to participate in the trial prior to any trial related assessments or procedures. 4. Must have measurable disease according to response assessment criteria relevant to the tumor type 5. Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1. 6. Must have acceptable laboratory parameters 7. A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception. |
1. Paciente con tumor o tumores sólidos localmente avanzados o metastásicos (excluyendo a los pacientes con tumores primarios del sistema nervioso central [SNC]), que hayan experimentado progresión de la enfermedad durante el tratamiento de referencia o sean intolerantes, o no aptos, al tratamiento de referencia. 2. Tener ≥18 años de edad. 3. El sujeto debe firmar un formulario de consentimiento informado (ICF) que indique que comprende el objetivo y los procedimientos requeridos para el ensayo y está dispuesto a participar en el ensayo antes de cualquier evaluación o procedimiento relacionado con el ensayo. 4. Presentar una enfermedad medible según los criterios de evaluación de respuesta pertinente para el tipo de tumor (p. ej., RECIST v1.1). 5. Presentar una puntuación del estado general del Grupo Oncológico Cooperativo del Este (EG de ECOG) de 0-1 en el momento de la selección y el día 1 del ciclo 1 (D1C1). 6. Debe tener parámetros de laboratorio aceptables. 7. Una mujer con potencial reproductivo debe aceptar usar un método anticonceptivo adecuado durante el ensayo y durante los 4 meses posteriores a la última administración de GEN1044. La anticoncepción adecuada se define como métodos anticonceptivos altamente efectivos. |
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E.4 | Principal exclusion criteria |
1. Has an uncontrolled intercurrent illness, including but not limited to: a. Ongoing or active infection requiring intravenous treatment with anti-infective therapy b. Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia. c. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management. d. Ongoing or recent evidence of significant autoimmune disease e. Subjects with a history of grade 3 or higher irAEs that led to treatment discontinuation f. Subjects with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade. g. History of chronic liver disease or evidence of hepatic cirrhosis. h. History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis. i. History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1044. j. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture. 2. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke. 3. Prior therapy: a. Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed. 4. Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved |
1. Presentar una enfermedad intercurrente no controlada, incluida entre otras: a. Infección en curso o activa que requiera tratamiento intravenoso con fármacos antiinfecciosos b. Insuficiencia cardíaca congestiva sintomática (de grado III o IV según la clasificación de la New York Heart Association), angina de pecho inestable o arritmia cardíaca. c. Hipertensión no controlada definida como presión arterial sistólica ≥160 mmHg y/ o presión arterial diastólica ≥100 mmHg, a pesar de un tratamiento médico óptimo. d. Indicios en curso o recientes de enfermedad autoinmunitaria significativa e. Se excluirá a los pacientes con antecedentes de AAri de grado 3 o superior que provocaran la interrupción del tratamiento f. Quedan excluidos del estudio los pacientes con antecedentes de miositis, síndrome de Guillain-Barré o miastenia gravis. g. Antecedentes de enfermedad hepática crónica o indicios de cirrosis hepática. h. Antecedentes de neumonitis no infecciosa que necesitó tratamiento con esteroides o neumonitis actual. i. Antecedentes de alotrasplante de órgano (excepto para el trasplante de córnea) o autólogo o alogénico de médula ósea, o rescate con células madre en los 3 meses previos a la primera dosis de GEN1044. j. Dificultad para la cicatrización de heridas grave, úlcera en la piel (de cualquier grado) o fractura ósea
2. Cualquier antecedente de malformación arteriovenosa intracerebral, aneurisma cerebral, metástasis cerebral nueva o sintomáticas o accidente cerebrovascular 3. Antes de la terapia a. Radioterapia: radioterapia dentro de los 14 días previos a la primera administración de GEN1044. Se permitirá la radioterapia paliativa. 4. Tratamiento con un agente anticancerígeno (dentro de los 28 días o después de al menos 5 vidas medias del medicamento, lo que sea más corto), antes de la administración de GEN1044. Toxicidades de terapias anticancerígenas anteriores que no se han resuelto. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation Part: • Dose-limiting Toxicities (DLTs) • Adverse events (AEs) and safety laboratory parameters
Dose Expansion Part: • Objective response rate (ORR) based on RECIST v1.1 |
Parte de aumento gradual de dosis: • Toxicidades limitantes de la dosis (TLD) • Acontecimientos adversos (AA) y parámetros analíticos de seguridad
Parte de expansión de la dosis: • TRO según los RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the trial, see protocol |
Durante el ensayo, ver protocolo |
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E.5.2 | Secondary end point(s) |
Dose Escalation Part): • PK parameters • Anti-drug antibody (ADA) response • Anti-tumor activity
Dose Expansion Part): • Anti-tumor activity • Progression free survival (PFS) • Overall survival (OS) • Adverse events (AEs) and safety laboratory parameters • PK parameters • Anti-drug antibody (ADA) response |
Parte de aumento gradual de dosis: • Parámetros FC • Respuesta de AAF • Actividad antitumoral
Parte de expansión de la dosis: • Actividad antitumoral • Supervivencia sin progresión (SSP) • Supervivencia general (SG). • AA y parámetros analíticos de seguridad • Parámetros FC • Respuesta de AAF |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During the trial, see protocol |
Durante el ensayo, ver protocolo |
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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 | 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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 6 |
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 |
Denmark |
Israel |
Spain |
United States |
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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 trial is considered completed when the last subject dies or withdraws from the trial. However, the maximum trial duration is 5 years after the last subject's first treatment in the trial. |
El ensayo se considera completado cuando el último sujeto muere o se retira del ensayo. Sin embargo, la duración máxima del ensayo es de 5 años después del primer tratamiento del último sujeto en el ensayo. |
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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 | 5 |
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 | 5 |
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 |