WCLC 2025 - Posters & ePosters-EP.06.67 Longitudinal ctDNA Profiling in HER2-Altered NSCLC Treated With HER2 Adc: Preliminary Results From the RESOLUTION Trial

EP.06.67 Longitudinal ctDNA Profiling in HER2-Altered NSCLC Treated With HER2 Adc: Preliminary Results From the RESOLUTION Trial

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The RESOLUTION trial (NCT06749860) investigated a novel combination therapy involving RC48, an antibody-drug conjugate targeting HER2, in treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring HER2 alterations. This phase II single-arm study integrated longitudinal circulating tumor DNA (ctDNA) profiling to non-invasively monitor tumor dynamics and treatment response. Nine patients provided 28 plasma samples collected at baseline and during treatment. Circulating cell-free DNA was analyzed using PredicineCARE for genomic variants and PredicineEPIC for genome-wide methylation profiling to estimate tumor fraction (TF) through somatic mutations, copy number variations (CNV), and methylation data.<br /><br />Results from April 2024 to July 2025 showed an objective response rate (ORR) of 55.5%, with five patients achieving partial response and four achieving stable disease. Baseline ctDNA profiling revealed diverse tumor-associated hotspot mutations among patients. Longitudinal analysis demonstrated that in responders, tumor fraction declined to undetectable levels by treatment cycle 5, while non-responders retained detectable tumor-derived ctDNA post-treatment, indicating persistent disease. These dynamics highlight ctDNA's utility as a real-time biomarker for assessing treatment efficacy and early detection of progression.<br /><br />The interim findings suggest that combining HER2-targeted ADC therapy with ctDNA monitoring offers a promising strategy for HER2-altered NSCLC. The study supports further investigation of this combination approach and validates longitudinal ctDNA analysis as a valuable non-invasive tool to dynamically track tumor burden and guide clinical decision-making in advanced NSCLC.

Asset Subtitle

Chunxia Su

Meta Tag

Speaker Chunxia Su

Topic Pathology and Biomarkers

Keywords

RESOLUTION trial

RC48

HER2 antibody-drug conjugate

non-small cell lung cancer

HER2 alterations

circulating tumor DNA

ctDNA profiling

tumor fraction

treatment response

longitudinal monitoring