LCMC LEADER neoadjuvant screening trial: LCMC4 evaluation of actionable drivers in early-stage lung cancers.

Abstract

TPS8596 Background: Comprehensive genomic profiling (CGP) has transformed the care of patients with advanced non-small cell lung cancer (NSCLC), giving many patients access to precision targeted treatment and immunotherapy with remarkable improvements in outcomes. Studies show that patients with lung cancers with oncogenic drivers are the least likely group to benefit from checkpoint inhibitors and are better served by enrollment in studies of targeted therapies. Early-stage NSCLC is now poised to benefit from these precision approaches with the regulatory approval of the first tyrosine kinase inhibitors and checkpoint inhibitors for the adjuvant treatment of resected NSCLC, each requiring testing for precision biomarkers. Neoadjuvant precision therapy for NSCLC has the potential to further improve treatment outcomes. Methods: The LCMC4 Evaluation of Actionable Drivers in EaRly Stage Lung Cancer (LEADER) Neoadjuvant Screening Trial (NCT04712877) is a collaborative diagnostic study developed by the Lung Cancer Mutation Consortium (LCMC), supported by the Thoracic Surgery Oncology Group and the Lung Cancer Research Foundation. The primary objective is to determine the proportion of patients with stage IA2-III lung cancers who possess actionable oncogenic drivers, defined as 1 of 11 actionable genomic alterations: mutations in EGFR, BRAFV600E, MET exon 14, KRAS G12C, and HER2, rearrangements in ALK, RET, NTRK, and ROS1, and amplification of MET and HER2. The study will also assess the feasibility of CGP to detect actionable oncogenic drivers in patients with suspected early-stage lung cancers scheduled to undergo biopsies to establish the diagnosis of lung cancer. The protocol will enroll 1000 patients with operable stage IA2-III (TNM 8th edition) lung cancer who will undergo CGP utilizing the Foundation Medicine 324 gene assay as well as paired liquid biopsy analysis. Results will enable selection of neoadjuvant therapy and enrollment onto independent therapeutic trials with genomically matched neoadjuvant treatment, standard therapies, or other trials if no driver is detected. The approach will be considered feasible if >35% of non-squamous NSCLCs have 1 of the 11 actionable alterations. Tumor mutational burden and PD-L1 IHC will be assessed. Plasma specimens collected pre- and post neoadjuvant treatment and post-surgery will be used for research to study the ability of circulating tumor DNA to assess neoadjuvant treatment response and minimal residual disease. 26 academic sites in the US plan to enroll patients. Clinical trial information: NCT04712877.