Genomic alterations in circulating tumor DNA (ctDNA) and response to telisotuzumab adizutecan (ABBV-400) treatment in patients (pts) with colorectal cancer (CRC).
Cecchini, M; Sharma, MR; Kuboki, Y; Perets, R; Cohen, J; Raimbourg, J; Nakajima, TE; Cruz-Correa, M; Ghiringhelli, F; Raghav, KPS; Luo, XA ...
Published in: Journal of Clinical Oncology
Telisotuzumab adizutecan is an antibody-drug conjugate comprising the c-Met–targeting antibody telisotuzumab conjugated to a topoisomerase 1 inhibitor payload, adizutecan. A phase 1 trial (NCT05029882) in advanced solid tumors reported higher response rates in pts with CRC and high c-Met expression. We present an analysis of responses based on genomic alterations in ctDNA.
Pts with CRC that is refractory to standard treatment were enrolled. Telisotuzumab adizutecan was given IV Q3W. ctDNA was isolated from baseline (BL) and cycle 3, day 1 plasma samples and analyzed with the GuardantINFINITY assay. Circulating tumor fraction (cTF) was estimated on the basis of variant allele frequency of somatic mutations in a 74-gene panel and methylation signals across targeted regions of the GuardantINFINITY methylation panel. Molecular response (MR) was defined as 50% decrease in cTF from BL. Radiographic response (RR) was assessed by RECIST v1.1.
Overall, 113 pts had both BL ctDNA and RR data. Confirmed ORR was 18% (20/113). The most prevalent gene alterations included
(75%),
(68%), and
(66%) mut;
(56%),
(53%), and
(52%) amp;
(44%) and
(43%) deletions; and
(4%),
,
and
(all 3%) fusions. The Table shows RRs in pts with specific CRC biomarkers, and MR using the 2 panels with corresponding clinical outcomes. RRs were seen in pts with positive plasma samples at BL for TMB,
and
MRs were detected in 64% and 65% of pts using the 74-gene and methylation panel, respectively. ORR was higher in pts with MR (35%) than without MR (8%) using the 74-gene, and 35% vs 0% using the methylation panel, respectively. Median PFS (mPFS) was longer in pts with MR.
Telisotuzumab adizutecan has promising efficacy. RRs were seen in CRC pts with heterogeneous genomic profiles, including pts positive for actionable biomarkers in the metastatic setting. More pts with MR experienced RRs and benefited from treatment.
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