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May 29, 2026Journal of Clinical Oncology

HER2-independent antitumor and pharmacodynamic responses to trastuzumab deruxtecan in patients with advanced solid tumors.

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Authors

SSSarah ShinGCGeraldine Helen O'Sullivan CoyneJFJared C. Foster

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Overview

Pilot study evaluates antitumor effects of trastuzumab deruxtecan in patients with varying HER2 expressions, indicating broad therapeutic potential.

Key Points

  • To determine pharmacodynamic responses and antitumor efficacy of trastuzumab deruxtecan in patients with advanced solid tumors and varying HER2 expression levels.
  • Multicenter pilot study with patients possessing advanced solid tumors and HER2 expression levels of 1+ or higher.
  • Patients received T-DXd (5.4 mg/kg intravenously every 3 weeks) along with tumor and blood samples for biomarker analysis.
  • Baseline HER2 expression was measured using immunohistochemistry across various patients.
  • Of 61 patients treated, 1 achieved a complete response and 14 showed confirmed partial responses despite differing HER2 status.
  • 15 of 21 biopsies indicated topoisomerase 1 target modulation, with 14 showing DNA damage repair induction.
  • Significant tumor infiltration and activation of CD8+ T cells were noted, correlating with patient responses.

Cite This Study

Shin et al. (2026) studied this question.

synapsesocial.com/papers/6a192e95fab5b468c4417b5bhttps://doi.org/10.1200/jco.2026.44.16_suppl.3031
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