Uncommon EGFR AZD9291

Non Small Cell Lung Cancer Clinical Trial

Official title: An Open Label, Multicenter, Phase II Single-arm Trial of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients With Uncommon Epidermal Growth Factor Receptor Mutations

Status Active, not recruiting

Clinical Trial Summary

EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations.

These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. In preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20 insertion mutation was fairly good.

Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.

Clinical Trial Description

This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9).

In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients.

Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

• NCT number: NCT03424759
• Study type: Interventional
• Source: Samsung Medical Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 1, 2016
• Completion date: July 31, 2019