2023 World Conference on Lung Cancer (Posters)-P2.10. Liquid Biopsy-based Umbrella Trial for Advanced NSCLC: Results of Phase 2 Plasma ALK-positive Cohort (A-Liquid)

P2.10. Liquid Biopsy-based Umbrella Trial for Advanced NSCLC: Results of Phase 2 Plasma ALK-positive Cohort (A-Liquid) - PDF(Abstract)

Back to course

Pdf Summary

Researchers conducted a phase 2 umbrella trial called A-Liquid, focused on patients with advanced non-small cell lung cancer (NSCLC) and oncogene alterations, using liquid next-generation sequencing (liquid NGS). The ALK cohort of this trial included ALK inhibitor-naïve patients with ALK rearrangements detected by liquid NGS. The primary endpoint was the objective response rate (ORR), determined by independent radiology review (IRR), with secondary endpoints including progression-free survival (PFS), overall survival (OS), and safety.<br /><br />From October 2019 to August 2021, tissue and liquid-based assays were performed on 5,197 patients. ALK, RET, and ROS1 fusions were identified in 61 (7.3%), 14 (1.7%), and 13 (1.6%) cases, respectively, by tissue-based assays. Liquid NGS revealed 37 cases of ALK fusions, 12 cases of RET fusions, and 3 cases of ROS1 fusions. The positive percent agreements (PPA) of liquid NGS for these fusion genes were 61% for ALK, 86% for RET, and 23% for ROS1.<br /><br />A total of 25 patients with ALK fusions detected by both tissue and liquid-based assays were enrolled in the A-Liquid trial. The objective response rate (ORR) by IRR was 100%, meeting the primary endpoint. The median PFS was 24.7 months, and the 12-month PFS rate was 73.9%. The median overall survival was not reached, and the 12-month overall survival rate was 96.0%. No new safety concerns were identified.<br /><br />The study shows that although the precision medicine approach using liquid NGS remains challenging due to the low positive percent agreements for fusion genes, alectinib is effective in a highly selected NSCLC population with ALK rearrangement detected by both tissue and liquid-based assays. Further analysis on resistance mechanisms using paired blood samples will be presented.<br /><br />Keywords: non-small cell carcinoma, liquid next-generation sequencing, ALK

Asset Subtitle

Yuki Nakatani

Meta Tag

Speaker Yuki Nakatani

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

non-small cell carcinoma

liquid next-generation sequencing

ALK

umbrella trial

oncogene alterations

ALK inhibitor-naïve patients

objective response rate

progression-free survival

overall survival

safety