TORC1/2 Inhibitor INK128 and EGFR Inhibitor AZD9291 in Treating Patients With Advanced 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 in Combination With 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 transducer of regulated CREB activity 1/2 (TORC1/2) inhibitor INK128 when given together with epidermal growth factor receptor (EGFR) inhibitor AZD9291in treating patients with advanced EGFR mutation positive non-small cell lung cancer that has spread to other places in the body (advanced) and has progressed after treatment with an EGFR tyrosine kinase inhibitor. TORC1/2 inhibitor INK128 and EGFR inhibitor AZD9291 may stop the growth of tumour cells by blocking some of the enzymes needed for cell growth.

Trial Description

Primary Outcome:

  • Dose-limiting toxicity (DLT) of TORC1/2 inhibitor INK128 in combination with EGFR inhibitor AZD9291 in patients with EGFRm NSCLC
  • MTD of TORC1/2 inhibitor INK128 in combination with EGFR inhibitor AZD9291 in patients with EGFRm NSCLC
Secondary Outcome:
  • Biomarkers of response and resistance to the combination, explored by studying baseline biopsies, resistance biopsies, and serial plasma DNA specimens
  • Disease control rate
  • Disease control rate of patients with T790M- NSCLC in an expansion cohort
  • Non-DLTs associated with the administration of TORC1/2 inhibitor INK128 and EGFR inhibitor AZD9291
  • Pharmacokinetic (PK) profiles of TORC1/2 inhibitor INK128 in combination with EGFR inhibitor AZD9291
  • Progression free survival
  • Progression free survival of patients with T790M- NSCLC in an expansion cohort
  • Response rate of patients with T790M- NSCLC in an expansion cohort, assessed using RECIST 1.1
  • Response rate, assessed using RECIST 1.1
PRIMARY OBJECTIVES:
  • To determine the safety and recommended phase II dose (RP2D) of MLN0128 (TORC1/2 inhibitor INK128) in combination with AZD9291 (EGFR inhibitor AZD9291) in patients with advanced epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC). (Dose escalation phase)
  • To evaluate the safety and preliminary efficacy of MLN0128 in combination with AZD9291 in patients with advanced EGFRm NSCLC that is negative for the resistance mutation T790M (T790M negative [-]). (Dose expansion phase)

SECONDARY OBJECTIVES:
  • To evaluate pharmacokinetic profiles of MLN0128 in combination with 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 TORC1/2 inhibitor INK128. Patients receive TORC1/2 inhibitor INK128 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 EGFR inhibitor AZD9291 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

Canadian Cancer Society

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