NCT02520778

Osimertinib and Navitoclax in Treating Patients With EGFR-Positive Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer

A Phase 1B Study of AZD9291 in Combination With Navitoclax in EGFR-Mutant Non-Small Cell Lung Cancer Following Resistance to Initial EGFR Kinase Inhibitor

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of osimertinib and navitoclax when given together and to see how well they work in treating patients with previously treated epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer that has spread to other places in the body (metastatic) or has not responded to previous treatment with initial EGFR kinase inhibitor. Osimertinib and navitoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of osimertinib (AZD9291) in combination with navitoclax in patients with EGFR-mutant non-small cell lung cancer (NSCLC) following resistance to prior EGFR-tyrosine kinase inhibitor (EGFR TKI). II. To evaluate the feasibility of treatment with AZD9291 plus navitoclax for patients with T790M-mediated acquired resistance to EGFR TKI. SECONDARY OBJECTIVES: I. To study the pharmacokinetic profile of the combination of AZD9291 plus navitoclax. II. To observe and record anti-tumor activity. CORRELATIVE OBJECTIVES: I. To study plasma genotype levels as a response biomarker in patients with EGFR-mutant lung cancer. II. To explore tissue biomarkers of apoptosis and their association with treatment response. OUTLINE: This is a phase Ib, dose-escalation study followed by a dose-expansion study. Patients receive navitoclax orally (PO) once daily (QD) on days 1-28 and osimertinib PO QD on days 4-28 (days 1-28 during dose-expansion). 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.

Conditions

• Advanced Lung Non-Squamous Non-Small Cell Carcinoma
• Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
• Stage III Lung Non-Small Cell Cancer AJCC v7
• Stage IIIA Lung Non-Small Cell Cancer AJCC v7
• Stage IIIB Lung Non-Small Cell Cancer AJCC v7
• Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

Type	Name	Description
DRUG	Navitoclax	Given PO
DRUG	Osimertinib	Given PO

Timeline

• Start date: 2016-08-30
• Primary completion: 2022-10-26
• Completion: 2023-12-04
• First posted: 2015-08-13
• Last updated: 2024-08-21

Locations

18 sites across 1 country: United States