Last updated: September 21, 2026
Sevabertinib (Hyrnuo, BAY 2927088) is an oral, reversible, small-molecule HER2 tyrosine kinase inhibitor (TKI), developed by Bayer. It targets activating mutations in HER2 (ERBB2) — including HER2 tyrosine-kinase-domain point mutations and exon 20 insertions. It was granted FDA accelerated approval on November 19, 2025 for HER2-mutant non-squamous NSCLC after prior systemic therapy, and that approval was expanded to the first-line setting on September 9, 2026. Recommended dose: 20 mg orally twice daily.
Mechanism of action:HER2 (ERBB2) activating mutations drive tumor growth in a subset of NSCLC. Sevabertinib is a reversible small-molecule TKI that blocks the intracellular kinase activity of mutant HER2, interrupting the growth-and-survival signals those mutations switch on. It is taken by mouth — the first oral targeted therapy for this molecular subset.
Regulatory status:FDA accelerated approval: November 19, 2025 (HER2-mutant non-squamous NSCLC after ≥1 prior systemic therapy), expanded to first-line September 9, 2026 (brand name Hyrnuo) — based on the SOHO-01 trial. As accelerated approvals, continued approval may be contingent on verification of clinical benefit in confirmatory trials (the Phase 3 NCT06452277 below). Solid tumors beyond NSCLC are investigational (basket trial ongoing, not FDA-approved).
About 2–4% of non-small cell lung cancers are driven by a mutation in a gene called HER2 (ERBB2). For years, patients with HER2-mutant lung cancer had few targeted options — and the first drug approved specifically for them, trastuzumab deruxtecan (Enhertu), is an antibody-drug conjugate given by intravenous infusion.
Sevabertinib is the first oral (pill) targeted therapy for HER2-mutant NSCLC. Instead of an infusion, it is a tablet taken twice a day that blocks the mutant HER2 protein's signaling from inside the cancer cell. That gives patients and their oncologists a new, mechanistically different option for the same molecular target.
What the trial showed. In the SOHO-01 study, sevabertinib shrank tumors in a large share of patients: among previously treated patients the confirmed response rate was 71%, and among first-line (treatment-naive) patients it was 75%. Those results supported the FDA's accelerated approval and its September 2026 expansion into first-line treatment. Because these are accelerated approvals, the ongoing Phase 3 confirmatory trial is important to verify long-term benefit.
Sevabertinib has 1 FDA-approved indication (HER2-mutant NSCLC), granted first for previously treated disease and then expanded to first-line.
HER2-Mutant Non-Squamous NSCLC — Previously Treated (initial accelerated approval)
HER2-Mutant Non-Squamous NSCLC — First-Line (September 2026 expansion)
★ First Oral Targeted Therapy for HER2-Mutant NSCLC
Before sevabertinib, the targeted option for HER2-mutant NSCLC was trastuzumab deruxtecan (Enhertu, T-DXd) — a HER2-directed antibody-drug conjugate that binds HER2 on the cell surface and delivers a chemotherapy (topoisomerase-inhibitor) payload, given by intravenous infusion. Sevabertinib works differently: it is a small-molecule TKI that blocks the intracellular kinase activity of mutant HER2, and it is taken orally.
This makes sevabertinib the first oral targeted therapy for the HER2-mutant NSCLC population — a pill-based alternative (or, potentially, a sequencing partner) to the infused antibody-drug conjugate. The two are different modalities against the same biomarker; treatment selection and sequencing are individualized decisions made with an oncology team.
Curated set of recruiting interventional sevabertinib / Hyrnuo / BAY 2927088 trials in the ClinTrialFinder corpus as of September 2026 (3 recruiting interventional trials), grouped by setting. SOHO-01 (NCT05099172) is the trial that supported the FDA approvals and continues to enroll.
HER2 (ERBB2) is a receptor tyrosine kinase on the cell surface. In a subset of NSCLC, activating mutations in the HER2 tyrosine-kinase domain — most commonly exon 20 insertions, along with certain point mutations — lock the receptor's kinase into a growth-promoting "on" state, independent of normal signals. Sevabertinib is a reversible, small-molecule tyrosine kinase inhibitor that binds mutant HER2 and blocks its intracellular kinase activity, cutting off the downstream growth-and-survival signaling those mutations drive. Because it acts on the kinase inside the cell (rather than delivering a chemotherapy payload from the cell surface, as an antibody-drug conjugate does), it can be given as an oral tablet.
On-Mechanism HER2 / ERBB Tyrosine-Kinase Effects
Inhibiting the HER2/ERBB tyrosine-kinase family carries characteristic, on-target side effects. Diarrhea is a hallmark effect of this drug class and is actively managed during treatment; rash and other gastrointestinal and skin effects are also commonly associated with HER2/EGFR-family TKIs. Sevabertinib is taken as an oral tablet (20 mg twice daily). Refer to the FDA prescribing information for the complete, sevabertinib-specific safety profile, monitoring, and dose-modification guidance.
These considerations are general to the HER2/ERBB tyrosine-kinase-inhibitor class and are not a substitute for the approved label. Your oncology team manages side-effect monitoring and any dose adjustments based on the official prescribing information and your individual situation.
In HER2 (ERBB2)-mutant advanced NSCLC, sevabertinib's September 2026 expansion means it can now be used in the first-line setting as well as after prior therapy — testing for a HER2 (ERBB2) activating mutation is what identifies eligible patients. It gives an oral targeted option alongside the HER2-directed antibody-drug conjugate trastuzumab deruxtecan (Enhertu, T-DXd), which is infused; selection and sequencing between them are individualized. For the broader HER2-targeting landscape, see the HER2 ADCs hub (note: that hub covers HER2 antibody-drug conjugates; sevabertinib is a HER2 TKI, a distinct modality). For the disease-level view, see the non-small cell lung cancer trials page.
What is sevabertinib (Hyrnuo) and how does it work?
Sevabertinib (Hyrnuo, BAY 2927088) is an oral, reversible, small-molecule tyrosine kinase inhibitor (TKI) from Bayer that targets activating mutations in HER2 (also called ERBB2), including HER2 tyrosine-kinase-domain point mutations and exon 20 insertions. By blocking the intracellular kinase activity of mutant HER2, it interrupts the growth signals those mutations drive. It is taken by mouth at a recommended dose of 20 mg twice daily.
What is sevabertinib FDA-approved for?
On November 19, 2025, the FDA granted accelerated approval to sevabertinib for adults with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) activating mutations and who had received a prior systemic therapy. On September 9, 2026, the FDA expanded the accelerated approval into the first-line setting, removing the prior-therapy requirement. It is the first oral targeted therapy approved specifically for HER2-mutant NSCLC.
What were the SOHO-01 trial results?
Both approvals are based on the Phase 1/2 SOHO-01 trial (NCT05099172). Among 70 previously treated patients, the confirmed objective response rate was 71%. In the first-line expansion cohort of 69 treatment-naive patients, the objective response rate was 75%, with 73% of responders maintaining a response for at least 6 months and 38% for at least 12 months. Because these are accelerated approvals, continued approval may depend on confirmatory trials.
How is sevabertinib different from trastuzumab deruxtecan (Enhertu, T-DXd)?
Both target HER2 in NSCLC, but by different mechanisms and routes. Trastuzumab deruxtecan (Enhertu, T-DXd) is a HER2-directed antibody-drug conjugate given by intravenous infusion; it binds HER2 on the cell surface and delivers a chemotherapy (topoisomerase-inhibitor) payload. Sevabertinib is an oral tyrosine kinase inhibitor that blocks the intracellular kinase activity of mutant HER2. Sevabertinib is the first oral targeted option for HER2-mutant NSCLC, offering a pill-based alternative to the infused antibody-drug conjugate.
Is sevabertinib being studied beyond lung cancer?
Yes. Recruiting trials include a Phase 3 first-line study versus standard of care in HER2-mutant advanced NSCLC (NCT06452277, the confirmatory trial); a Phase 2 open-label basket study in metastatic or unresectable HER2-mutant advanced solid tumors beyond lung cancer (NCT06760819); and SOHO-01 (NCT05099172), the first-in-human Phase 1/2 study in advanced NSCLC with EGFR and/or HER2 mutations that continues to enroll.
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