P47.11 COMPEL: Chemotherapy With/Without Osimertinib in Patients With EGFRm Advanced NSCLC and Progression on First-Line Osimertinib

Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR TKI-sensitizing T790M resistance mutations with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), including central nervous system (CNS) metastases. the preferred first-line treatment EGFRm advanced NSCLC; however, progression eventually occurs. Guidelines recommend upon systemic progression, osimertinib be discontinued platinum-based doublet chemotherapy initiated. Tumor heterogeneity means while some tumor cells become osimertinib-resistant, others may remain sensitive. Continued during beneficial compared alone, particularly patients CNS metastases given has superior chemotherapy. In addition, continuing prevent rebound phenomenon. COMPEL (NCT04765059) will evaluate safety of versus placebo NSCLC who experienced non-CNS following therapy. phase III, randomized, double-blind, placebo-controlled study (Figure). Eligible patients: adults (age, ≥18 years); WHO PS 0–1; life expectancy >12 weeks; non-squamous (Ex19del/L858R) locally advanced, metastatic or recurrent NSCLC. Patients must have radiological evidence initial response to osimertinib; clinical on are ineligible. Approximately 204 randomized (1:1) across arms, stratified per presence absence stable Arm A receive pemetrexed plus cisplatin carboplatin (plat-pem; investigator’s choice; 75 mg/m2, AUC5, 500 mg/m2) 80 mg, followed by maintenance mg/m2 mg. B plat-pem placebo, placebo. first dose within four weeks their last dose. Serial imaging chest, abdomen brain required. Treatment continue until RECIST 1.1- 1.1-defined another discontinuation criterion met. post-progression provided they benefit. Cross-over from allowed if confined CNS. The primary objective compare progression-free survival (PFS). PFS individually evaluated as secondary endpoints, overall survival. Safety also reported. First patient enrolled expected April 2021; results September 2024. ▪▪▪