What question did this study set out to answer?

To demonstrate the effectiveness of trastuzumab deruxtecan combined with zongertinib in overcoming drug resistance in HER2 mutated NSCLC.

May 15, 2026Lung Cancer Targets and Therapy0 citationsOpen Access

HER2-ADC and HER2-TKI Overcomes HER2 Amplification as an Acquired Resistance to Zongertinib – A Case Report

MNMisako Nagasaka ZAZhaohui Arter CPC H Park

Key Points

To demonstrate the effectiveness of trastuzumab deruxtecan combined with zongertinib in overcoming drug resistance in HER2 mutated NSCLC.
Case report of a patient with HER2 mutated NSCLC
Combination therapy of trastuzumab deruxtecan and zongertinib after progression on each agent alone
Patient responded positively to the combination therapy after previously failing solo treatments
Tumor progression was halted, highlighting the effectiveness of the new regimen

Abstract

Abstract: Trastuzumab deruxtecan, zongertinib and sevabertinib have been approved in the United States for the treatment of patients with advanced metastatic HER2 mutated non–small-cell lung cancer (NSCLC). Unfortunately, tumor progression is inevitable in many cases. In this case report, we share our experience with a patient with HER2 mutated NSCLC who responded to the combination of trastuzumab deruxtecan and zongertinib after progressing on each agent when given alone, highlighting the potential for such combinations. Keywords: trastuzumab deruxtecan, T-Dxd, combination therapy, HER2 mutation, mechanism of resistance

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