Abstract 563: cfDNA-based analysis of minimal residual disease and T-cell receptor clonality as predictors of relapse in stage 3 NSCLC treated with chemoradiotherapy and durvalumab

Introduction: Durvalumab immunotherapy has rapidly emerged as standard treatment for stage 3 NSCLC patients following definitive chemoradiotherapy (CRT). Multiple novel immunotherapeutic strategies are in development to enhance the chance of cure in this setting as well. There exists a critical need to identify blood-based biomarkers capable of predicting clinical benefit from adjuvant immunotherapy as well selecting patients at high-risk of relapse for further drug development. Cell-free DNA (cfDNA)-based analysis of both minimal residual disease (MRD) and T-cell receptor (TCR) clonality have immense potential to predict and monitor response to adjuvant immunotherapy. In this study, we have combined innovative cfDNA measures of MRD (CAPPseq), TCR clonality (CapTCR-seq) and methylation (cfMeDIPseq) as potential predictive biomarkers of disease progression in stage 3 NSCLC patients treated with CRT and durvalumab. Methods: Stage 3 NSCLC patients undergoing CRT and durvalumab were recruited prospectively to undergo serial blood collections at baseline, pre- and post- durvalumab. CAPPseq and cfMeDIPseq were performed as measures of MRD. TCR repertoire analysis (CapTCR-seq) was performed on cfDNA using hybrid-capture TCR sequencing and TCR diversity/clonality was estimated using the Shannon's index. Correlations between MRD, TCR clonality, response and progression-free survival (PFS) were examined using logistic/cox regression. Results: 79 stage 3 NSCLC patients have been prospectively recruited and undergone serial blood collection. CAPPseq, cfMeDIPseq and capTCR-seq have been completed in 22 patients (5 primary progression on CRT, 17 received durvalumab). Tumor cfDNA was detectable by CAPPseq at baseline in 14 patients. High correlation between tumor cfDNA detected by CAPPseq and cfMeDIPseq was found (R=0.68, p