The US FDA has granted accelerated approval to Hyrnuo (sevabertinib) for the first-line treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations. The approval, which followed Priority Review and Breakthrough Therapy Designation, extends Bayer's existing accelerated approval for sevabertinib — previously granted in November 2025 for previously treated patients in the same biomarker-defined population — into the treatment-naive setting.
The indication requires HER2 mutation detection by an FDA-authorized test. Continued approval may be contingent on confirmatory results from the ongoing Phase III SOHO-02 trial (NCT06452277), which is evaluating sevabertinib against standard of care in treatment-naive patients with advanced HER2-mutated NSCLC.
Sevabertinib is an oral, reversible small molecule tyrosine kinase inhibitor (TKI) that selectively targets mutated HER2 — including exon 20 insertions and point mutations — and mutated EGFR, while sparing wild-type EGFR. Bayer said the compound was derived from its research alliance with the Broad Institute of MIT and Harvard.
The accelerated approval rests on data from Cohort F of the Phase I/II SOHO-01 trial (NCT05099172), enrolling 69 treatment-naive patients with locally advanced or metastatic non-squamous HER2-mutated NSCLC. The primary endpoints were objective response rate (ORR) and duration of response (DOR). The reported ORR was 75% (95% CI: 64–85), with complete responses in 6% and partial responses in 70% of patients; 73% of responders maintained response for at least six months and 38% for at least 12 months. The most common adverse reactions (>20%) were diarrhea, rash, stomatitis, paronychia, nausea, and weight decrease.
Sevabertinib enters a first-line HER2-mutated NSCLC landscape that now includes at least one other oral TKI. Boehringer Ingelheim's zongertinib (Hernexeos) received US FDA accelerated approval in the first-line HER2-mutated NSCLC setting in February 2026, as previously reported. Both agents are oral, mutation-selective HER2 TKIs. The FDA's Priority Review applied to the supplemental new drug application for this biomarker-defined population, which accounts for an estimated 2% to 4% of advanced NSCLC cases per the company's cited literature.
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