A Phase I/II Study of AZD9291 (Osimertinib) and CB-839 Hydrochloride HCl in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

Summary

This interventional study, which is open to patient accrual at Ohio State, will examine the side effects and best dose of the glutaminase inhibitor CB-839 hydrochloride (HCI), and will also see how well this agent works when given together with osimertinib in treating patients with stage IV non-small cell lung cancer (NSCLC) and a mutation in the EGFR gene. Treatment with the glutaminase inhibitor CB-839 HCI and osimertinib may stop the growth of tumor cells by interfering with the enzymes used by cancer cells for growth.

Study Design

Patients receive glutaminase inhibitor CB-839 hydrochloride orally twice daily and osimertinib once daily (starting cycle 1 day 16 of phase I). 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. The estimated study completion date is
June 1, 2021.

Primary Objectives

1. To assess the safety and tolerability of this drug combination and recommend a phase II dose for patients with metastatic EGFR-activating mutation-positive NSCLC;
2. To determine the efficacy of this combination in patients who have developed progressive disease on front-line EGFR inhibitor therapy.

Secondary Objectives

1. To determine toxicity profile of the combination of AZD9291 and CB-839 HCl (telaglenastat) in patients with metastatic EGFR-activating mutation-positive NSCLC. (Phase I)
2. To assess the pharmacokinetics of CB-839 HCl (telaglenastat) and AZD9291 in patients with metastatic EGFR-activating mutation positive. (Phase I)
3. To determine progression-free survival of AZD9291 and CB-839 HCl (telaglenastat) in patients with EGFR mutation-positive, T790M mutation-negative NSCLC who have developed progressive disease (PD) on front-line EGFR inhibitor therapy. (Phase II)
4. To determine the overall survival (OS) of AZD9291 and CB-839 HCl (telaglenastat) in patients with EGFR mutation-positive, T790M mutation-negative NSCLC who have developed PD on front-line EGFR inhibitor therapy. (Phase II)

Study Leader

Principal investigator for this clinical trial is Dwight Owen, MD, assistant professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Questions and trial referrals should be directed to katie.dicostanzo@osumc.edu.

At a Glance

Trial No.: OSU-19016
gov identifier: NCT03831932
PI: Dwight Owen, MD
Phone: (614) 685-2039
Email: Dwight.Owen@osumc.edu

Eligibility: Men and women 18 years of age or older; ability to swallow pills; life expectancy greater than three months; histologically confirmed stage IV NSCLC, with advanced or metastatic disease; activating mutation present in the EGFR gene (L858R or exon 19 deletion, alone or in combination with other EGFR mutations) as per local assessment of a tissue biopsy specimen obtained since the time of disease progression on prior therapy; must have had progressive disease on prior EGFR inhibitor therapy (gefitinib, erlotinib, afatinib or osimertinib); no limit to lines of prior tyrosine kinase inhibitor (TKI) therapy; (other eligibility requirements and exclusion criteria may be viewed at OSU-19016).