FDA Approves Sevabertinib in HER2-Mutated Nonsquamous NSCLC

The FDA has granted an accelerated approval to sevabertinib (Hyrnuo) for the treatment of adult patients with previously treated locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC) whose tumors harbor HER2 tyrosine kinase domain (TKD) mutations as detected by an FDA-approved test.¹

The approval was based on results from the open-label, single-arm, multicenter SOHO-01 trial (NCT05099172), in which sevabertinib had an objective response rate (ORR) of 71% in a population of 70 patients with unresectable or metastatic, nonsquamous NSCLC with HER2 TKD activating mutations who had prior systemic therapy but had not received HER2-targeted therapy. The median duration of response (DOR) in these patients was 9.2 months and 54% of responders had a DOR of more than 6 months.

In a subgroup of 52 patients whose prior therapy had included a HER2-targeted antibody drug conjugate, the ORR was 38%, with a median DOR of 7.0 months. Among the responders, 60% reached a DOR of 6 months or higher.

Safety data for sevabertinib showed that the treatment was tolerable with a manageable adverse event profile. Nearly all patients (97.4%) experienced at least 1 treatment-related adverse event (TRAE) with diarrhea being the TRAE most commonly resulting in a dose reduction. However, diarrhea did not lead to treatment discontinuation in any patients. No patients had interstitial lung disease.

Sevabertinib is an oral, reversible TKI that inhibits mutant HER2, including HER2 exon 20 insertions and HER2 point mutations, along with mutant EGFR.

Overall, the SOHO-01 trial was an open-label, first-in-human phase 1/2 study enrolling adults with recurrent or metastatic NSCLC that had progressed following at least 1 prior systemic regimen. To enroll in the trial, patients had to have documented EGFR and/or HER2 mutations, measurable disease (RECIST 1.1 criteria), an ECOG performance status of 0 or 1, adequate bone marrow and organ function, and a minimum life expectancy of 12 weeks.

FDA Label Notes and Next Steps

The FDA label for sevabertinib recommends that the treatment be dosed at 20 mg orally with food twice daily until disease progression or unacceptable toxicity. The prescribing information also lists warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.

Since sevabertinib was approved under the FDA’s accelerated approval program, continued approval of the treatment is contingent upon results from a confirmatory trial.

The ongoing phase 3 SOHO-02 trial (NCT06452277) is assessing sevabertinib as a first-line treatment option for patients with HER2-mutant NSCLC. Sevabertinib is also being evaluated in patients with metastatic or unresectable solid tumors harboring HER2-activating mutations (excluding advanced NSCLC) in the phase 2 panSOHO study (NCT06760819).

Simultaneously with the approval of sevabertinib, the FDA also approved the companion diagnostic Oncomine Dx Target Test, which can facilitate detection of HER2 TKD activating mutations in patients with nonsquamous NSCLC who may be candidates for receiving sevabertinib.

Earlier this year when the FDA granted a priority review to the application for sevabertinib, Christine Roth, executive vice president, global product strategy and commercialization and member of the pharmaceutical’s leadership team at Bayer, stated in a news release, “Patients with HER2-mutant NSCLC are predominantly women, may be of younger age and nonsmokers. The FDA’s decision to grant priority review designation to our application for sevabertinib is a significant milestone that validates both the unmet need and the potential for sevabertinib to fulfill that need.”²

REFERENCES

1. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. US FDA. November 19, 2025. Accessed November 19, 2025. https://tinyurl.com/wyesray4

2. Sevabertinib (BAY 2927088) granted FDA Priority Review for the treatment of patients with HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed November 19, 2025. https://tinyurl.com/3whzs7jt