Resumen

Este es un estudio global para evaluar los efectos de osimertinib en participantes con CPCNP con mutación EGFR en estadio IA2-IA3 tras la resección tumoral completa.

Descripción detallada

Este es un estudio internacional de Fase III, doble ciego, aleatorizado, controlado con placebo, de 2 brazos, que evalúa la eficacia y seguridad de osimertinib adyuvante versus placebo en participantes con CPCNP de histología no escamosa en estadio IA2-IA3 con mutación EGFR que han sido sometidos previamente a resección tumoral completa. Todos los participantes deben haber tenido un tumor que albergue una de las 2 mutaciones EGFR comunes asociadas con sensibilidad a los inhibidores de EGFR-TKI (Ex19del, L858R). Los participantes elegibles serán aleatorizados en proporción 1:1 a uno de los 2 brazos de intervención: osimertinib 80 mg o placebo equivalente, una vez al día durante 3 años, salvo que se cumplan los criterios de discontinuación.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Male or female, at least ≥ 18 years.
NSCLC, of non-squamous histology.
Stage IA2 or IA3 disease, based on TNM8 classification.
Complete surgical resection (R0) of the primary NSCLC by lobectomy, bilobectomy, segmentectomy or sleeve resection.
Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants.
World Health Organization performance status of 0 or 1.
Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.
A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test.
Minimum life expectancy of \> 6 months.
Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception.

Criterios de exclusión

Mixed small cell and non-small cell cancer history.
Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy or only wedge resection.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including HCV and HIV or active uncontrolled HBV infection.
History of another primary malignancy, including any known or suspected synchronous primary lung cancer except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.
Any of the following cardiac criteria:
Mean resting QTcF interval \> 470 ms, obtained from triplicate ECGs performed at screening.
Any abnormalities in rhythm, conduction, or morphology of resting ECG,
Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events.
History of interstitial lung disease.
Inadequate bone marrow reserve or organ function.
Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.
Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs).
Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.
Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.

Intervenciones

drug

Osimertinib

The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease recurrence, unacceptable toxicity or other discontinuation criteria are met.

drug

Placebo

Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Osimertinib

Placebo

Ubicaciones

Research Site

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Patrocinadores