Sevabertinib is an oral, reversible HER2 inhibitor, selective for wild-type EGFR, active against HER2 mutations including exon 20 insertions, point mutations and ERBB2 amplification[1][2]. These mutations occur in 2 to 4% of lung adenocarcinoma patients[1]. The phase 1/2 SOHO-01 study (NCT05099172) tested sevabertinib as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) with HER2 mutations after prior systemic therapy[2][3]. In 70 patients with HER2 TKD mutations without prior HER2-targeted therapy, the objective response rate (ORR) was 71% and the median duration of response (DOR) was 9.2 months, with 54% of responders having a DOR of more than 6 months[3][6]. In 52 patients after prior HER2-targeted treatment with antidotes, the ORR was 38% with a median DOR of 7.0 months[6]. The FDA granted accelerated approval of sevabertinib on November 19, 2025 for adult patients with locally advanced or metastatic nonsquamous NSCLC with HER2 TKD mutations confirmed by an FDA-approved test after prior systemic therapy[3][6]. The most frequent adverse effect was diarrhea, which did not lead to treatment termination [3]. Preclinical data confirm activity also in models with neuregulin-1 fusion [1].