TOP: A phase III, multicentre, randomized controlled study comparing osimertinib in combination with carboplatin and pemetrexed to osimertinib monotherapy for untreated patients with advanced non-squamous (Non-sq) non-small cell lung cancer (NSCLC) with concurrent EGFR and TP53 mutations.

• DOI: 10.1200/jco.2024.42.16_suppl.tps8662
• Publication Date: 2024-06-12T14:26:24Z
• Authors: Yunpeng Yang; Weineng Feng; Wei Jiang; Lu Huang; Yanqiu Zhao; Lili Chen; Yong Fang; Mei Ji; Tingting Zhang; Junfei Zhu; Li Zhang
• Keywords: Osimertinib; Pemetrexed; Carboplatin

TPS8662 Background: Osimertinib is the current standard first-line treatment for advanced non-sq NSCLC with sensitive EGFR mutations. However, previous studies demonstrated that patients concurrent and TP53 mutations had suboptimal clinical benefit EGFR-TKI monotherapy. FLAURA2 study showed osimertinib plus pemetrexed platinum-based chemotherapy significantly improved progression-free survival (PFS) compared monotherapy EGFR-mutated patients. Further needed to better understand benefits of model The objective this determine whether could improve efficacy in Mutations. Methods: This a phase III, randomized, open-label trial Non-sq harboring (exon 19 deletion or L858R) mutations, performance status 0 1, planned receive therapy. Eligible will be randomized 1:1 arm (osimertinib 80 mg orally per day) combination therapy day 500 mg/m 2 carboplatin area under curve 5 intravenously every 3 weeks four cycles, followed by maintenance osimertinib). Randomization stratified PS score (0 vs. 1), brain metastases (yes no) mutation type L858R). primary end point PFS RECIST 1.1 assessed investigator. Secondary points include overall survival, response rate, duration response, adverse events quality life. Exploratory endpoint correlation between other than efficacy, resistance mechanisms revealed dynamic ctDNA profiling. Approximately 170 required detect hazard ratio 0.65 80% power at two-sided significance level 0.05. 292 enrolled. Until February 2024, 204 have been enrolled, last patient expected enrolled June 2024. Clinical information: NCT04695925 .