Zongertinib + T-DXd Shows Early Responses in Trastuzumab-Pretreated HER2+ mGEAC

Zongertinib is an oral, irreversible HER2-selective TKI designed to spare wild-type EGFR, here combined with trastuzumab deruxtecan (T-DXd), a HER2-directed topoisomerase I ADC, in Cohort C of the Phase Ib/II Beamion BCGC-1 trial (NCT06324357). In unresectable/metastatic HER2+ gastric/GEJ/esophageal adenocarcinoma after prior HER2-directed therapy, the combination produced confirmed responses, including CR/PRs across dose levels, with 1 CR and multiple PRs reported; this compares against T-DXd monotherapy benchmarks in post-trastuzumab HER2+ gastric/GEJ cancer of ~42% ORR and ~5.6-month mPFS in DESTINY-Gastric02. Safety was meaningful but not prohibitive in this small cohort: any-grade/G≥3 TEAEs were 89%/47%, zongertinib-related G≥3 AEs were 11%, and there was 1 case each of grade 1 pneumonitis and ILD that recovered.