Sapanisertib and Osimertinib in Treating Patients With Stage IV EGFR Mutation Positive Non-small Cell Lung Cancer After Progression on a Previous EGFR Tyrosine Kinase Inhibitor

Official Title

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

Summary:

This phase I trial studies the side effects and best dose of sapanisertib when given together with osimertinib in treating patients with stage IV EGFR mutation positive non-small cell lung cancer that has progressed after treatment with an EGFR tyrosine kinase inhibitor. Sapanisertib and osimertinib may stop the growth of tumour cells by blocking some of the enzymes needed for cell growth.

Trial Description

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, assessed using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
  • Disease control rate
  • Progression free survival
  • Response rate of patients with T790M- NSCLC in an expansion cohort, assessed using RECIST 1.1
  • 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:
I. 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) who are resistant to previous EGFR-tyrosine kinase inhibitor (TKI) therapy. (Dose escalation phase) II. To evaluate the safety and preliminary efficacy of MLN0128(TAK-228) in combination with osimertinib (AZD9291) in patients with advanced EGFRm NSCLC that is negative for the resistance mutation T790M (T790M negative [-]) and who are resistant to previous EGFR-TKI therapy. (Dose expansion phase) SECONDARY OBJECTIVES:
I. To evaluate pharmacokinetic profiles of MLN0128 (TAK-228) in combination with osimertinib (AZD9291). II. To evaluate the response rate, disease control rate and progression free survival of the combination. III. 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 course 1). Patients also receive osimertinib PO QD on days 1-28. Courses 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.

View this trial on ClinicalTrials.gov

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Resources

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