Abstract 1479P
Background
ctDNA is validated across multiple indications for identification of actionable mutations and detection of minimal residual disease. We evaluated if TARgeted DIgital Sequencing (TARDIS) may distinguish PR from CR with in mRCC patients (pts) receiving immune checkpoint inhibitor (ICI) therapy.
Methods
Eligible pts had pathologically confirmed mRCC that yielded a PR or CR to ICI therapy. Peripheral blood was obtained at a single time point for ctDNA analysis. TARDIS, a novel bespoke assay capable of ascertaining up to 100 patient-specific founder mutations via whole genome sequencing, was used for quantification of variant allele fractions (VAFs). Our primary objective was to determine the association between VAFs and depth of response (PR versus CR). A secondary objective was to determine if VAFs were associated with disease progression on subsequent imaging, which was obtained using computed tomography as part of routine care. Mann–Whitney U tests were used for the comparison of means between two datasets.
Results
A total of 12 pts (8:4 M:F) were analyzed, most of whom achieved a PR (75%). Pts received either nivolumab monotherapy (50%) or nivolumab plus ipilimumab (50%). Most pts had clear cell histology (92%). ctDNA analysis incorporated an average of 30 patient-specific mutations (range 19-35); average coverage depth was 103,342 read families per sample. TARDIS quantified a significant difference in VAFs between PR and CR (p=0.018). Additionally, six pts demonstrated radiographic progression subsequent to ctDNA assessment. TARDIS reached a significant difference in VAFs between those with sustained radiographic response and those who progressed on subsequent imaging (p=0.026).
Conclusions
TARDIS was able to accurately differentiate PR from CR amongst pts with mRCC receiving ICIs, and also prospectively identified pts at risk for subsequent progression. Given these findings, we envision subsequent studies that utilize this assay to identify appropriate candidates for ICI discontinuation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
City of Hope Comprehensive Cancer Center.
Funding
Has not received any funding.
Disclosure
N. Dizman: Non-Financial Interests, Personal, Invited Speaker: Vivreon Gastroscience Inc. T. Dorff: Financial Interests, Personal, Advisory Board: Seagen, AbbVie, AstraZeneca; Financial Interests, Institutional, Advisory Board: Exelixis; Financial Interests, Personal, Other, drafted educational content (unbranded): Astellas; Financial Interests, Institutional, Research Grant: Pfizer. M. Murtaza: Non-Financial Interests, Institutional, Invited Speaker: PetDx, Castle Biosciences, AstraZeneca. S.K. Pal: Non-Financial Interests, Personal, Invited Speaker: Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen, Astellas, Bristol Myers Squibb. All other authors have declared no conflicts of interest.