E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with EGFR-mutant advanced NSCLC with progression on previous third generation EGFR TKI |
Pacientes con NSCLC avanzado con mutación de EGFR con progresión en TKI de EGFR de tercera generación anterior |
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E.1.1.1 | Medical condition in easily understood language |
Patients with non-small cell lung cancer that: • Has a change (mutation) in a gene called EGFR • Has spread to other parts of the body during, or after treatment with osimertinib or lazertinib. |
Pacientes con cáncer de pulmón de células no pequeñas: • Con mutación en un gen llamado EGFR • Se ha propagado a otras partes del cuerpo durante/ después del tratamiento con osimertinib o lazertinib |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The primary objective of the trial is to assess the efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or lazertinib), in patients with EGFR-mutant advanced NSCLC, who have been previously treated with a third-generation EGFR-TKI in order to provide data on treatment effect and sample size required for a future phase III trial. |
El objetivo principal del ensayo es evaluar la eficacia de amivantamab y bevacizumab combinados al tratamiento continuado con un EGFR-TKI de tercera generación (osimertinib o lazertinib), en pacientes con CPNM avanzado con mutación de EGFR, que han sido tratados previamente con un tercer EGFR-TKI de última generación para proporcionar datos sobre el efecto del tratamiento y el tamaño de la muestra necesarios para un futuro ensayo de fase III. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate secondary measures of clinical efficacy including progression-free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR).
-To assess the safety and tolerability of the treatment. |
- Evaluar medidas secundarias de eficacia clínica, incluida la supervivencia libre de progresión (PFS), la supervivencia general (OS), la duración de la respuesta (DoR), la tasa de control de la enfermedad (DCR).
-Evaluar la seguridad y tolerabilidad del tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or stage IV according to 8th TNM classification 2. Presence of the sensitising EGFR-mutation (only patients with exon 19 deletion and/or L858R are eligible) and documentation of T790M status, tested locally by an accredited laboratory. 3. Radiologically confirmed disease progression on previous treatment with osimertinib or lazertinib. Treatment with osimertinib or lazertinib must have been stopped at least 8 days before enrolment. 4. Achieved objective clinical benefit from osimertinib or lazertinib treatment (e.g., documented PR/ CR or SD for ≥6 months while on osimertinib or lazertinib treatment). 5. Measurable disease as defined according to RECIST v1.1. 6. Age ≥18 years. |
1. NSCLC no escamoso confirmado histológicamente, estadio IIIB/C (no susceptible de tratamiento radical) o estadio IV según la 8ª clasificación TNM 2. Presencia de la mutación sensibilizante de EGFR (solo los pacientes con deleción del exón 19 y/o L858R son elegibles) y documentación del estado T790M, probado localmente por un laboratorio acreditado. 3. Progresión de la enfermedad confirmada radiológicamente en un tratamiento previo con osimertinib o lazertinib. El tratamiento con osimertinib o lazertinib debe haberse interrumpido al menos 8 días antes de la inscripción. 4. Logró un beneficio clínico objetivo del tratamiento con osimertinib o lazertinib (p. ej., PR/CR o SD documentados durante ≥6 meses durante el tratamiento con osimertinib o lazertinib). 5. Enfermedad medible según la definición de RECIST v1.1. 6. Edad ≥18 años. |
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E.4 | Principal exclusion criteria |
1. Patients with known small cell lung carcinoma (SCLC) transformation. 2. Patients with symptomatic brain metastases. Patients with asymptomatic or previously treated and stable brain metastases may participate in this study. Patients who have received definitive radiotherapy or surgery for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at ≥2 weeks before enrolment are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to enrolment. 3. Patients with an active or past medical history of leptomeningeal disease. 4. Patients with untreated spinal cord compression. Patients who have been definitively treated with surgery or radiotherapy and have a stable neurological status for ≥2 weeks prior to enrollment are eligible provided they are off corticosteroid treatment or are receiving low-dose corticosteroid treatment ≤10 mg/day prednisone or equivalent. 5. Patients with unresolved adverse events (other than alopecia) from prior anticancer therapy that have not resolved to grade ≤1 or baseline. 6. Patients with positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) test. |
1. Pacientes con transformación conocida de carcinoma de pulmón de células pequeñas (CPCP). 2. Pacientes con metástasis cerebrales sintomáticas. Los pacientes con metástasis cerebrales asintomáticas o previamente tratadas y estables pueden participar en este estudio. Los pacientes que hayan recibido radioterapia definitiva o cirugía por metástasis cerebrales sintomáticas o inestables y que hayan estado clínicamente estables y asintomáticos durante ≥2 semanas antes de la inscripción son elegibles, siempre que hayan estado sin tratamiento con corticosteroides o estén recibiendo tratamiento con corticosteroides en dosis bajas (≤10 mg/día de prednisona o equivalente) durante al menos 2 semanas antes de la inscripción. 3. Pacientes con antecedentes médicos activos o pasados de enfermedad leptomeníngea. 4. Pacientes con compresión de la médula espinal no tratada. Los pacientes que han sido tratados definitivamente con cirugía o radioterapia y tienen un estado neurológico estable durante ≥2 semanas antes de la inscripción son elegibles siempre que no estén en tratamiento con corticosteroides o estén recibiendo tratamiento con corticosteroides en dosis bajas ≤10 mg/día de prednisona o equivalente. 5. Pacientes con eventos adversos no resueltos (aparte de la alopecia) de una terapia anticancerosa anterior que no se hayan resuelto a un grado ≤1 o al valor inicial. 6. Pacientes con prueba de antígeno de superficie (HBsAg) positiva para hepatitis B (virus de la hepatitis B [VHB]). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR), investigator assessed, at 12 weeks according to RECIST v1.1 |
• Tasa de respuesta objetiva (TRO) a las 12 semanas según RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
interim analysis (1 year) and final analysis (2 years) |
análisis intermedio (1 año) y análisis final (2 años) |
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E.5.2 | Secondary end point(s) |
1. Duration of response (DoR) 2. Progression-free survival (PFS) according to RECIST v1.1 3. Disease control rate (DCR) according to RECIST v1.1 4. Overall survival (OS) 5. Safety and tolerability (CTCAE v5.0) |
• Duración de la respuesta (DdR) • Supervivencia sin progresión (SSP) según RECIST v1.1 • Tasa de control de la enfermedad (TCE) según RECIST v1.1 • Supervivencia global (SG) • Seguridad y tolerabilidad (CTCAE v5.0) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
final analysis (2 years) |
Análisis final (2 años) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Korea, Republic of |
Singapore |
France |
Netherlands |
Spain |
Switzerland |
Italy |
United Kingdom |
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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
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LPLV |
última visita del último paciente |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |