FDA Grants Accelerated Approval to Sevabertinib for HER2-Mutated Non-Squamous NSCLC
Key Clinical Summary
- Design/Population: On November 19, 2025, the US FDA granted accelerated approval to sevabertinib for adults with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations after prior systemic therapy. The decision was supported by the SOHO-01 trial (NCT05099172)—an open-label, single-arm, multicenter, multi-cohort study enrolling previously treated patients with HER2-mutant NSCLC.
- Key Outcomes: In 70 HER2 therapy–naïve patients, ORR was 71% (95% CI, 59–82) with median DOR 9.2 mo; 54% maintained response ≥6 mo. In 52 HER2-pretreated patients, ORR was 38% (95% CI, 25–53) with median DOR 7.0 mo; 60% had response ≥6 mo. The Oncomine Dx Target Test was simultaneously approved as a companion diagnostic.
- Clinical Relevance: Sevabertinib (20 mg PO BID) provides a targeted option for HER2-mutant NSCLC with meaningful responses across treatment histories. Label warnings include diarrhea, hepatotoxicity, ILD/pneumonitis, ocular and pancreatic toxicity, and embryo-fetal risk.
On November 19, 2025, the US Food and Drug Administration (FDA) granted accelerated approval to sevabertinib for the treatment of adult patients with locally advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC) with HER2 tyrosine kinase domain (TKD) activating mutations, detected by an FDA-approved test, and who have received prior systemic therapy.
In addition to this approval, the FDA has also approved the Oncomine Dx Target Test as a companion diagnostic tool to identify HER2 TKD activating mutations among patients with non-squamous NSCLC eligible for treatment with sevabertinib, a kinase inhibitor.
This approval was based on results from the SOHO-01 (NCT05099172) trial, an open-label, single-arm, multicenter, multi-cohort study that enrolled patients with unresectable or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations who had received prior systemic therapy. Mutation status was determined in tumor tissue or plasma by local laboratories prior to enrollment.
The primary efficacy outcomes were confirmed objective response rate (ORR) and duration of response (DOR). Among 70 patients included patients who were naïve to HER2 mutation targeting therapy, the ORR was 71% (95% confidence interval [CI], 59 to 82), with a median DOR of 9.2 months (95% CI, 6.3 to 5.0). Among patients who responded to treatment, 54% maintained a response for 6 months.
Among 52 patients who had received prior systemic therapy including HER2-targeted antibody–drug conjugates, the ORR was 38% (95% CI, 25 to 53), with a median DOR of 7.0 months (95% CI, 5.6 to not evaluable), and 60% of responders had a DOR of ≥6 months.
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
Source:
US Food and Drug Administration. Accessed on November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
