ctDNA analysis
Plasma samples were collected from patients at baseline at each cycle of treatment. ctDNA analysis was performed using Tempus xF (Tempus). Germline and CHIP variants were filtered by comparison with targeted sequencing of matched PBMCs. Artifacts and additional suspected germline variants were removed by manual curation. To be considered monitorable, individual variants had to have a VAF of >0.5% at any timepoint, and patients had to have at least one variant with a VAF of >1% at any timepoint. The mVAF was calculated for each timepoint for each patient, and then the mVAF ratio (mVAFR) of each on-treatment timepoint relative to baseline was calculated. For patients with multiple on-treatment timepoints, the best mVAFR was selected. Patients with ≥50% reduction in mVAFR from baseline for at least one timepoint were considered molecular responders.