E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer |
Cáncer de pulmón de células no pequeñas avanzado o metastásico con mutación de EGFR |
|
E.1.1.1 | Medical condition in easily understood language |
A specific type of lung cancer called "Non-Small Cell Lung Cancer" |
Un tipo específico de cáncer de pulmón llamado "Cáncer de Pulmón de Células no Pequeñas" |
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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 | 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) |
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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 |
Primary objectives are: Part 1: To assess the noninferiority of amivantamab SC-CF administered via manual injection (Arm A1) versus amivantamab IV (Arm B1) Part 2: To assess the bioequivalence of amivantamab SC-CF administered via manual injection (Arm A2) and amivantamab SC-CF OBDS (Arm B2) |
Los objetivos primarios son: Parte 1: Evaluar la no inferioridad de amivantamab SC-CF administrado mediante inyección manual (Brazo A1) frente a amivantamab IV (Brazo B1) Parte 2: Evaluar la bioequivalencia de amivantamab SC-CF administrado mediante inyección manual (Brazo A2) y amivantamab SC-CF OBDS (Brazo B2) |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess: 1. Efficacy of amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2) 2. Safety of amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2) 3. Amivantamab pharmacokinetics and immunogenicity to amivantamab or rHuPH20 in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2) 4. Cancer therapy satisfaction in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS(Arm B2) 5. Time and motion analysis in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2)
Refer the protocol for all secondary objectives |
1.Eficacia de amivantamab SC-CF administrado mediante inyección manual (Brazos A1 y A2) frente a amivantamab IV (B1) o amivantamab SC-CF OBDS (B2) 2.Seguridad de amivantamab SC-CF administrado mediante inyección manual (A1 y A2) frente a amivantamab IV (B1) o amivantamab SC-CF OBDS (B2) 3.Farmacocinética e inmunogenicidad de amivantamab frente a amivantamab o rHuPH20 en participantes tratados con amivantamab SC-CF administrado mediante inyección manual (A1 y A2) frente a amivantamab IV (B1) o amivantamab SC-CF OBDS (B2) 4.Grado de satisfacción con la terapia del cáncer en participantes tratados con amivantamab SC-CF administrado mediante inyección manual (A1 y A2) frente a amivantamab IV (B1) o amivantamab SC-CF OBDS (B2) 5.Análisis de tiempo y movimiento en participantes tratados con amivantamab SC-CF administrado mediante inyección manual (A1 y A2) frente a amivantamab IV (B1) o amivantamab SC-CF OBDS (B2) Consulte el protocolo para todos los objetivos secundarios |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study: 1. Be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent 2. Have histologically or cytologically confirmed, advanced or metastatic NSCLC, characterized by either EGFR Exon 19del or Exon 21 L858R mutation by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor 3. Have progressed on or after osimertinib and platinum-based chemotherapy (irrespective of order). •Osimertinib must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. •Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. •Any adjuvant or neoadjuvant treatment, whether with osimertinib or platinum-based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease progression within 6 months of the last dose. 4. Have at least 1 measurable lesion, according to RECIST v1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6. Have adequate organ and bone marrow function as follows, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test: •Hemoglobin ≥9 g/dL •Absolute neutrophil count ≥1.5×10^9/L, without use of granulocyte colony stimulating factor (G-CSF) within 10 days prior to the date of the test •Platelets ≥75×10^9/L, •ALT and aspartate aminotransferase (AST) ≤3×upper limit of normal (ULN) if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases. •Total bilirubin •≤1.5×ULN if no demonstrated liver metastasis • ≤3×ULN in the presence of liver metastasis •≤3×ULN for those participants with known Gilbert’s syndrome with conjugated [direct] bilirubin <1.5xULN. •Creatinine clearance >50 mL/min as measured or calculated by Modified Diet in Renal Disease (MDRD) 7. Human immunodeficiency virus-positive participants are eligible if they meet all of the following: a. No detectable viral load (ie, <50 copies/mL) at screening b. CD4+ count >300 cells/mm^3 at screening c. No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening d. Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening Note: HAART that could interfere with study treatment is excluded 8. Any toxicities from prior anticancer therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade ≤2 peripheral neuropathy, and Grade ≤2 hypothyroidism stable on hormone replacement) 9. A female participant of childbearing potential must have a negative serum pregnancy test at screening and must agree to further serum or urine pregnancy tests within 72 hours of the first dose, during the study, and for 7 months after the last dose of study treatment 10. A female participant must be either of the following: a. Not of childbearing potential, or b. Of childbearing potential and practicing at least 1 highly effective method of contraception, throughout the study and through 7 months after the last dose of study treatment. Note: If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with (b.).
Refer the protocol for all the inclusion criteria. |
1. Tener ≥18 años. 2. Presentar confirmación histológica o citológica de CPNM avanzado o metastásico EGFR positivo por deleción del exón 19 o sustitución del exón 21 L858R, caracterizado por un test aprobado por la FDA u otra prueba validada en un laboratorio certificado por CLIA (centros en EE. UU.), o en un laboratorio local acreditado (centros fuera de EE. UU.) Una copia del informe de la mutación tiene que ser incluida en los registros del paciente y una copia anonimizada tiene que ser enviada al promotor. 3. Haber progresado a o después de osimertinib y quimioterapia basada en platino (independientemente del orden). Ver detalles adicionales en la sección 5.1 del Protocolo. 4. Tener al menos una lesión medible, de acuerdo con los criterios RECIST v1.1. Si la única lesión diana ha sido previamente irradiada, tiene que mostrar signos de progresión. 5. ECOG de 0 a 1. 6. Tener una función adecuada de los órganos y la médula ósea, sin tener antecedentes de transfusión de glóbulos rojos o transfusión de plaquetas en los 7 días anteriores a la fecha del análisis de laboratorio. Ver detalles adicionales en la sección 5.1 del Protocolo. 7. Los pacientes con VIH positivo son elegibles, siempre y cuando cumplan con las condiciones detalladas en la sección 5.1 del Protocolo. 8. Cualquier toxicidad del tratamiento antineoplásico previa, debe haberse resuelto según los Criterios CTCAE V.5. 0 a grado 1 o nivel basal. Ver excepciones en la sección 5.1 del Protocolo.
9. Las mujeres en edad fértil deben presentar una prueba de embarazo en suero negativa en la selección y aceptar la realización de más pruebas de embarazo en suero u orina las 72 horas anteriores a la primera dosis, durante el estudio y hasta 7 meses después de la última dosis.
10. Las mujeres tienen que estar dentro de cualquiera de las siguientes situaciones (ver Apéndice 5 del Protocolo): a. No ser fértil. b. Ser fértil y utilizar al menos 1 método anticonceptivo de alta eficacia durante el estudio y hasta 7 meses después de la última dosis (ver Apéndice 5 del Protocolo).
11. Las mujeres deben comprometerse a no donar óvulos (ovocitos) ni a congelarlos para el futuro con fines de reproducción asistida durante el estudio y durante 7 meses después de recibir la última dosis del tratamiento del estudio.
12. Los hombres deben utilizar preservativo al realizar cualquier actividad que permita el paso del esperma eyaculado a otra persona durante el estudio y durante un mínimo de 7 meses después de recibir la última dosis del tratamiento del estudio. Si la pareja del hombre es una mujer en edad fértil, el hombre participante tiene que utilizar preservativo y su pareja también tiene que utilizar un método anticonceptivo de alta eficacia (ver apéndice 5). Si el participante se ha sometido a una vasectomía, tiene que utilizar preservativo, pero no se requiere que su pareja utilice un método anticonceptivo. 13. Los pacientes de sexo masculino deben comprometerse a no donar esperma con fines de reproducción durante el estudio y al menos 7 meses después de haber recibido la última dosis del tratamiento del estudio. 14. Firmar un Consentimiento Informado (o su representante legal) indicando que el participante entiende el propósito y los procedimientos requeridos para el estudio y está dispuesto a participar en el mismo. 15. Estar dispuesto y ser capaz de adherirse a las restricciones en el estilo de vida especificadas en el protocolo. |
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E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1. Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors, as allowed in Inclusion criterion 3. 2. Participant has a history of uncontrolled illness, including but not limited to the following: •Uncontrolled diabetes •Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection) •Active bleeding diathesis •Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of study treatment •Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements •Any ophthalmologic condition that is clinically unstable. 3. Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization. 4. Participant has symptomatic or progressive brain metastases. Participants with treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 2 weeks prior to randomization are eligible. 5. Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation. 6. Participant has uncontrolled tumor-related pain. Symptomatic lesions amenable to palliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the randomization. 7. Participant has a medical history of ILD, including drug-induced ILD or radiation pneumonitis. 8. Have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). 9. Participant has a history of hypersensitivity to any of the excipients of amivantamab, lazertinib, or to rHuPH20. 10. Participant has a history of clinically significant cardiovascular disease including, but not limited to, the following: •Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment, or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary. •Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). •Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg •Congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III-IV or Hospitalization for CHF (any NYHA class) within 6 months of randomization •Pericarditis/clinically significant pericardial effusion •Myocarditis 11. Participant had major surgery (eg, requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before signing the ICF, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
Refer the protocol for all the exclusion criteria. |
1. Haber recibido algún tratamiento citotóxico, en investigación o terapias dirigidas más allá de un régimen basado en platino y un inhibidor de EGFR, como se permite en el Criterio de Inclusión 3.
2. Tener una enfermedad no controlada. Ver detalles en sección 5.2 del Protocolo.
3. Haber recibido radioterapia paliativa menos de 7 días antes de la aleatorización.
4. Pacientes con metástasis cerebrales sintomáticas o progresivas. Pacientes con metástasis tratadas, que sean clínicamente estables y asintomáticas las 2 últimas semanas y para las que no se ha recibido dosis bajas de corticosteroides durante las 2 últimas semanas antes de la aleatorización, son elegibles.
5. Tener enfermedad leptomeníngea o compresión de la médula espinal que no se haya tratado definitivamente con cirugía o radiación.
6. Tener dolor no controlado relacionado con el tumor.
7. Historia de enfermedad intersticial pulmonar, incluyendo la inducida por fármacos o neumonitis por radiación.
8. Tener una neoplasia previa o concurrente (diferente a la de este estudio) cuya historia o tratamiento pueda interferir con los endpoints de seguridad o eficacia (ver Apéndice 16 del Protocolo).
9. Historia de hipersensibilidad a los excipientes de amivantamab, lazertinib o rHuPH20.
10. Enfermedad cardiovascular clínicamente significativa. Ver más detalles en Sección 5.2 del Protocolo.
11. Cirugía mayor previa en las últimas 4 semanas antes de la firma de consentimiento informado. Ver más detalles en Sección 5.2 del Protocolo.
12. Durante la selección: ser seropositivo para Hepatitis B, tener anticuerpos positivos de Hepatitis C en los últimos 3 meses antes de empezar el tratamiento de estudio (NOTA: si los anticuerpos son positivos por una enfermedad previa resuelta, se podrá incluir al paciente con una prueba negativa de ARN), prueba positiva de ARN para hepatitis C en la selección o 3 meses antes de la primera dosis u otra infección hepática clínicamente activa.
13. Haber recibido una vacuna viva o viva atenuada en los 3 meses antes de la aleatorización. La vacuna de la gripe estacional y las no vivas contra COVID-19 no excluyen.
14. Estar recibiendo suplementos o medicaciones que se conozcan como inductores potentes del CYP3A4/5 y no poder discontinuarlos con un periodo de lavado adecuado antes de la aleatorización (ver Apéndice 11 del Protocolo).
15. Haber participado previamente en los estudios del promotor 73841937NSC3003 (NCT04487080) o 61186372NSC3002 (NCT04988295). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: Arm A1 vs Arm B1 1. Ctrough of amivantamab at steady state 2. AUCD1-D15 Part 2: Arm A2 vs Arm B2 3. Cmax of amivantamab 4. AUCD1-D8 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: Arm A1 vs Arm B1 1. Cycle 4 Day 1 2. Cycle 2 Part 2: Arm A2 vs Arm B2 3. After Cycle 1 Day 1 4. Cycle 1 |
|
E.5.2 | Secondary end point(s) |
1. Overall response rate (ORR) 2. Progression-free survival (PFS) 3. Duration of response (DoR) 4. Time to response (TTR) 5. Incidence and severity of adverse events and clinical laboratory abnormalities 6. Incidence and severity of IRR 7. Ctrough of amivantamab (Part 1) 8. Model Predicted AUCD1-D15 (Part 1) 9. Ctrough of amivantamab (Part 2) 10. The presence of anti-amivantamab antibodies and anti-rHuPH20 antibodies 11. Modified TASQ 12. Change from baseline assessed over time 13. Participant chair time 14. Participant time in treatment room 15. Duration of treatment administration 16. Active HCP time for drug preparation, treatment administration, and post treatment monitoring. 17. Rate of successful injections with amivantamab SC-CF OBDS by HCP 18. Ease of Use and Satisfaction Questionnaire completed by HCP |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. From randomization until the date of objective disease progression or death, whichever comes first 5-6. Throughout the study 7. Cycle 2 Day 1 8. Cycle 4 9. Cycle 4 Day 1 10. Day 1 of Cycle 1, 2, 3, 4, 5, 7, 9,11, EOT 11-12. Cycle 1 Day 1, Cycle 1 Day 2, Cycle 3 Day 1, EOT 13-16. Day 1 of Cycle 1 and 3 17. At each amivantamab SC-CF administration 18. Cycle 2 Day 1 |
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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 | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Immunogenicity and Biomarker evaluations |
Evaluaciones de tolerabilidad, inmunogenicidad y biomarcadores |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Not a controlled study but parallel groups: IMP SC-CF vs IMP IV (1) and IMP SC-CF vs IMP SC-OBDS(2) |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Taiwan |
Thailand |
United States |
France |
Poland |
Spain |
Germany |
Italy |
Portugal |
Turkey |
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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12 months after the last participant has been randomized |
12 meses después de que el último participante haya sido asignado al azar. |
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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 | 3 |
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 | 3 |