Prognostic and predictive value of ultrasensitive ctDNA monitoring in a metastatic pan-cancer cohort treated with immune checkpoint inhibitors in the context of phase 1 clinical trials.

• DOI: 10.1200/jco.2024.42.16_suppl.2510
• Publication Date: 2024-06-17T13:58:12Z
• Authors: Rodrigo De Almeid...; Alma M Calahorro ...; Oriol Mirallas; Ana Moreno; Vladimir Galvao; Guzmán Alonso; Maria Vieito; Irene Brana; Arjun Oberoi; M. Julia Lostes-B...; Jose Jimenez; Marta Sanz; Cristina Viaplana; Raquel Perez-Lopez; Paolo Nuciforo; Charles Abbott; Jason Pugh; Richard Chen; Sean Michael Boyle; Elena Garralda
• Keywords: 03 medical and health sciences; 0302 clinical medicine

2510 Background: Determining which patients will achieve clinical benefit from immune checkpoint inhibition (ICI) therapy remains an open question. Liquid biopsy tests to assess baseline and early dynamics of circulating tumor DNA (ctDNA) may allow clinicians track response more granularly predict ICI or resistance prior imaging. However, lack sensitivity hinder accurate detection low ctDNA levels in tumors with shedding rates during substantial drops clearance response. Methods: This study represents a cohort 175 refractory metastatic 18 different cancer types, who received 1-3 successive lines treatment the context phase-1 trials. Thus far, 609 plasma samples 90 stage-IV receiving inhibitor have been processed. was profiled using NeXT Personal assay, liquid platform that leverages whole-genome sequencing normal create custom, patient-specific panels include up 1,800 somatic variants. enables molecular residual disease (MRD) down threshold 1 part per million (PPM) ctDNA. Results: assay detected positive 99% (81/82) samples, wide dynamic range, extending 4.2 PPM (~0.00042% TF) ~640,000 (~64% (median limit = 2 PPM, 0.0002% TF). Lower values at were correlated increased duration PFS (log-rank p=0.017, HR=0.57, 95% CI 0.36-0.91) extended OS p=0.002, HR=0.46, 0.28-0.75). Early reduction level cycle 3 associated significant increases p=0.001, HR=0.36, 0.19-0.67) p=0.015, HR=0.44, 0.22-0.87), representing >3-fold increase both median OS. resulted improvement (PFS: log-rank HR=0.24, 0.09-0.62; OS: p=0.01, HR=0.29, 0.1-0.8). All timepoints periods durable complete (CR) assessed via RECIST 1.1 ctDNA-negative, lead time 277 days over radiographically confirmed CR. Conclusions: We demonstrate are predictive long-term advanced, pan-cancer ECT setting. Even this advanced cohort, ultra-sensitive required for MRD status determination, detections might otherwise missed. Taken together, these findings suggest high is crucial monitoring response, providing information patient management.