Antitumor Activity of Trastuzumab Deruxtecan in Pediatric Solid Tumors with Variable HER2 Expression.

ABSTRACT: Trastuzumab deruxtecan (T-DXd) is an ERBB2/HER2-targeting antibody-drug conjugate (ADC) with efficacy across adult cancers exhibiting variable HER2 expression. Prior studies demonstrating HER2 expression in osteosarcoma motivated a clinical trial of T-DXd in pediatric and adolescent/young adults with osteosarcoma, but the trial was terminated early because of inactivity. We evaluated the activity of T-DXd using osteosarcoma patient-derived xenograft (PDX) models and found a 22% objective response rate despite no detectable HER2 expression across PDXs tested. To further assess non-HER2-mediated activity, we evaluated the activity of T-DXd across 31 pediatric cancer cell lines and found osteosarcoma to be amongst the most resistant to T-DXd, as well as unconjugated deruxtecan, providing a po

SUBMITTER: Burke CM 

PROVIDER: S-EPMC12490493 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature