The FDA has expanded the accelerated approval of sevabertinib (Hyrnuo) for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have certain activating HER2 (ERBB2) mutations. Eligible patients must have a HER2 mutation in the tyrosine kinase domain (TKD), identified with an FDA-authorized test.
The expanded approval now allows Hyrnuo to be used for eligible patients regardless of whether they have received prior systemic therapy for advanced cancer. Previously, Hyrnuo was available only after a patient had received prior systemic treatment. This change may allow some people with HER2-mutated NSCLC to receive this oral targeted therapy earlier in their treatment journey.
What Hyrnuo targets
Non-squamous NSCLC includes lung adenocarcinoma, the most common subtype of lung cancer. Comprehensive biomarker testing is important because some tumors have gene changes that can help guide treatment decisions.
HER2, also called ERBB2, is a gene that can become altered in some lung cancers. Certain HER2 TKD activating mutations can send growth signals that help cancer cells multiply. Hyrnuo is an oral kinase inhibitor, meaning it is designed to block abnormal signaling from HER2 and slow or stop cancer-cell growth.
Hyrnuo is intended for a specific group of patients with HER2-mutated NSCLC; it is not a treatment for all lung cancers or all HER2-positive cancers.
Study results supporting expansion
The FDA’s expanded approval was based on results from the ongoing SOHO-01 clinical trial, an open-label study of sevabertinib in people with locally advanced or metastatic non-squamous NSCLC with HER2 TKD activating mutations.
Among 69 patients who had not previously received systemic therapy for advanced disease:
- 75% had a confirmed response to treatment, meaning their tumors shrank or were no longer detectable on scans.
- Among people whose cancer responded, 73% had a response lasting at least 6 months.
- Among people whose cancer responded, 38% had a response lasting at least 12 months.
Earlier SOHO-01 findings also supported the original approval in patients who had already received systemic treatment. In one previously treated group that had not received a HER2-targeted therapy before, about 71% of 70 patients had tumor shrinkage, with a median response duration of 9.2 months. In another group of 52 patients previously treated with a HER2-targeted antibody–drug conjugate, about 38% responded and the median response duration was 7.0 months.
Understanding accelerated approval
Accelerated approval is an FDA pathway intended to make promising treatments available sooner for serious conditions with unmet medical need. In this case, the approval was based on measures such as the proportion of patients whose tumors responded and how long those responses lasted.
Continued approval of Hyrnuo may depend on additional studies confirming clinical benefit, such as whether treatment helps people live longer, delays cancer progression, or performs favorably compared with other treatment strategies.
Side effects and monitoring
Hyrnuo can cause side effects, including some that may be serious. The prescribing information includes warnings and precautions for:
- Diarrhea
- Liver problems, also called hepatotoxicity
- Lung inflammation, including interstitial lung disease or pneumonitis
- Changes in heart function, including left ventricular dysfunction
- Eye-related side effects
- Increases in pancreatic enzymes on blood tests
- Potential harm to an unborn baby during pregnancy
Patients should contact their cancer care team promptly for new or worsening diarrhea, cough, shortness of breath, fever, vision changes, yellowing of the skin or eyes, severe abdominal pain, chest symptoms, or unusual fatigue. The oncology team may monitor laboratory tests, symptoms, heart function, and eye health during treatment.news.cancerconnect
Questions for your care team
If you have locally advanced or metastatic non-squamous NSCLC, you may want to ask:
- Has my tumor received comprehensive biomarker testing?
- Do I have a HER2/ERBB2 TKD activating mutation?
- Was my HER2 result identified using an FDA-authorized test?
- Am I eligible to receive Hyrnuo before other systemic treatment for advanced disease?
- How does Hyrnuo compare with chemotherapy, immunotherapy, or other targeted-treatment options for my cancer?
- What side effects should I report right away?
- Are clinical trials appropriate for me?
The expanded approval reinforces why biomarker testing matters in advanced NSCLC. Finding an actionable mutation, such as a qualifying HER2 alteration, can help patients and their care teams consider treatment options tailored to the biology of the cancer.
References
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-smallnon-squamous-non-small-cell-lung-cancer?utm_medium=email&utm_source=govdelivery
Le X, Kim TM, Loong HH, et al; SOHO-01 Investigators. Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2025 Nov 6;393(18):1819-1832.
