Zongertinib Irreversible HER2 TKI Posts 27% ORR with Zero ≥G3 Toxicity in Refractory HER2-Driven MBC

Zongertinib is a covalent HER2 tyrosine-kinase inhibitor. In the Phase Ia dose-escalation study (NCT04886804) 15 heavily pre-treated stage IV breast cancer patients with HER2 amplification/over-expression or mutation received BID or QD (part of 121-patient all-tumor cohort. Confirmed objective responses were 4 PRs for a 26.7% ORR (unconfirmed 46.5%) and 73.3% disease control; two responses remained on therapy at data cut-off. Grade ≥3 adverse events occurred in 12.4%. The single-agent activity is on par with neratinib’s ~29% ORR and median PFS 4.5 mo, where ≥G3 diarrhea hits 28%, and exceeds capecitabine’s typical 20–40% ORRin salvage settings with notable hand–foot syndrome.