Initial results of a screening trial for evaluating oncogenic drivers in Japanese patients with surgically resected early-stage non-small cell lung cancer: LC-SCRUM-Advantage.

8065 Background: The LC-SCRUM-Advantage is a screening trial to evaluate oncogenic drivers in patients with surgically resected early-stage non-small cell lung cancer (NSCLC). Recent clinical trials, such as the ADAURA and ALINA trials, have demonstrated the efficacy of molecular targeted therapy as adjuvant therapy following surgery for patients with early-stage NSCLC harboring oncogenic drivers. Our study aims to determine the proportion of early-stage NSCLC with any actionable oncogenic drivers that are candidates for adjuvant targeted therapy. This abstract presents the initial data collected until Dec 2024. Methods: Patients with operable clinical stage I to III NSCLC were eligible for this study. Surgical tumor samples were collected post-surgery, and genomic analysis of oncogenic drivers was centrally evaluated using a next-generation sequencing system, the Oncomine Precision Assay, which targets 50 gene alterations. PD-L1 immunohistochemistry using the 22C3 antibody was also performed on the submitted tumor samples. If possible, preoperative biopsy tumor samples were also collected and evaluated using the AmoyDx Pan Lung Cancer PCR Panel. An actionable oncogene was defined as EGFR, ALK, ROS1, KRAS, BRAF, HER2, RET, MET, NRG1, or NTRK genes. Results: Between August 2022 and December 2024, 646 patients were enrolled in the LC-SCRUM-Advantage. Among them, 57% had stage I, 27% had stage II, 16% had stage III, and 71% had adenocarcinoma histology. Of the 591 evaluable patients in this analysis, an actionable oncogenic driver was found in 46% of cases (274/591). Identified oncogenic drivers included 190 (24%) EGFR mutations (89 L858R, 77 ex19del, 10 ex20ins, 14 uncommon), 26 (4%) MET ex14 skipping, 20 (3%) KRAS G12C, 18 (3%) HER2 mutations (including ex20ins), 7 (1%) ALK fusion, 5 (1%) NRG1 fusion, 4 (1%) BRAFV600E, 2 (<1%) RET fusions, 1 (<1%) ROS1 fusion, and 1 (<1%) NTRK fusion. PD-L1 expression was observed in 19% for >50%, 40% for 1-49%, and 41% for <1%. Among patients with paired tumor samples from surgery and preoperative biopsy, the concordance rate of detected actionable oncogenic drivers was 95%. Conclusions: Our study found actionable oncogenic drivers in 46% of Japanese patients with surgically resected early-stage NSCLC. Based on historical control, the proportion of any oncogenic drivers in early-stage NSCLC is similar to that in advanced NSCLC. Comprehensive genomic screening of patients with early-stage NSCLC will accelerate the development of clinical trials for adjuvant-targeted therapy.