Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer

Titre officiel

A Phase 1 Trial of MLN0128 (TAK-228) in Combination With Osimertinib (AZD9291) in Advanced EGFR Mutation Positive Non-Small Cell Lung Cancer (NSCLC) After Progression on a Previous EGFR Tyrosine Kinase Inhibitor

Sommaire:

Cet essai de phase I porte sur les effets secondaires et la meilleure dose de transducteur de l’inhibiteur de l’activité régulée de CREB 1/2 (TORC1/2), soit l’INK128, administrée en association avec l’inhibiteur du récepteur de facteur de croissance épidermique (EGFR), soit l’AZD9291, dans le cadre d’un traitement de patients atteints d’un cancer du poumon non à petites cellules présentant une mutation du gène de l’EGFR, qui s’est propagé vers d’autres régions de l’organisme (stade avancé) et qui a progressé après un traitement par un inhibiteur de la tyrosine kinase de l’EGFR. L’inhibiteur du TORC1/2, soit l’INK128, et l’inhibiteur de l’EGFR, soit l’AZD9291, peuvent stopper la croissance des cellules tumorales en bloquant certaines enzymes nécessaires à la croissance cellulaire.

Description de l'essai

Primary Outcome:

• Maximum tolerated dose of sapanisertib in combination with osimertinib in patients with EGFRmutant (m) non-small cell lung cancer (NSCLC)
• Dose-limiting toxicity (DLT) of sapanisertib in combination with osimertinib in patients with EGFRm NSCLC

Secondary Outcome:

• Non-DLTs associated with the administration of sapanisertib and osimertinib
• Pharmacokinetic (PK) profiles of sapanisertib in combination with osimertinib
• Response rate
• Disease control rate
• Progression free survival
• Response rate of patients with T790M- NSCLC in an expansion cohort
• Disease control rate of patients with T790M- NSCLC in an expansion cohort
• Progression free survival of patients with T790M- NSCLC in an expansion cohort
• Biomarkers of response and resistance to the combination, explored by studying baseline biopsies, resistance biopsies, and serial plasma deoxyribonucleic acid specimens

PRIMARY OBJECTIVES:

• To determine the safety and recommended phase II dose (RP2D) of sapanisertib (MLN0128) (TAK-228) in combination with osimertinib (AZD9291) in patients with advanced epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC) and who are resistant to previous EGFR-tyrosine kinase inhibitor (TKI) therapy. (Dose escalation phase)
• To evaluate the safety and preliminary efficacy of MLN0128 (TAK-228) in combination with osimertinib (AZD9291) in patients with advanced EGFRm NSCLC who are resistant to previous EGFR-TKI therapy with first line osimertinib. (Dose expansion phase)

SECONDARY OBJECTIVES:

• To evaluate pharmacokinetic profiles of MLN0128 (TAK-228) in combination with osimertinib (AZD9291).
• To evaluate the response rate, disease control rate and progression free survival of the combination.
• To explore biomarkers of response and resistance to the combination by studying baseline biopsies, resistance biopsies, and serial plasma deoxyribonucleic acid (DNA) specimens.

OUTLINE:
This is a dose-escalation study of sapanisertib. Patients receive sapanisertib orally (PO) once daily (QD) on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (day 1 is omitted in cycle 1). Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 8 weeks thereafter.

Voir cet essai sur ClinicalTrials.gov