Phase IB study to evaluate efficacy and tolerability of olaparib (AZD2281) plus gefitinib in patients (P) with epidermal growth factor receptor (EGFR) mutation positive advanced non-small cell lung cancer (NSCLC) (NCT=1513174/GECP-GOAL).

Abstract

8079 Background: Progression-free survival (PFS) and response rate (RR) to EGFR tyrosine kinase inhibitors (TKIs) vary in P with NSCLC driven by EGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. High BRCA1 mRNA expression negatively influenced PFS among EGFR mutant P treated with erlotinib. We hypothesized that since olaparib can attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve PFS in these P. Methods: This is a Phase IB dose escalation study (standard 3+3 design) to identify the maximum tolerated dose (MTD), dose limiting toxicity (DLT), pharmacokinetics (PK), and clinical activity of orally administered olaparib in combination with gefitinib in EGFR mutant advanced NSCLC. P were treated with gefitinib 250mg once daily plus olaparib at escalating doses ranging from 100mg BID to 250mg TDS during a 28-day cycle. Results: Twenty-two P were included across four dose levels of olaparib: 100mg BID (3), 200mg BID (6), 200mg ...