The U.S. Food and Drug Administration (FDA) has approved a new targeted therapy called HYRNUO (sevabertinib) for some adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have a specific HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutation and who have already received prior systemic therapy. This is an accelerated approval, which means the decision is based on how well the drug shrank tumors and how long those responses lasted in a clinical trial, and continued approval will depend on confirming longer-term benefit in further studies.
What the SOHO-01 trial showed
HYRNUO was studied in the SOHO-01 trial, which enrolled people with unresectable or metastatic non-squamous NSCLC whose tumors had HER2 TKD activating mutations and who had previously received systemic treatment. In one group of 70 patients who had not received prior HER2-targeted therapy, about 71% had their tumors shrink (objective response rate), and these responses lasted a median of 9.2 months, with just over half of responders staying in response for at least 6 months.
In another group of 52 patients who had already been treated with HER2-targeted antibody–drug conjugates, about 38% had tumor shrinkage, and the median duration of response was 7.0 months, with 60% of responders maintaining their response for at least 6 months. These results suggest HYRNUO may offer a meaningful option for people whose cancer carries this specific HER2 mutation, including some who have already tried other HER2‑targeted treatments.
Safety and what patients should know
As with many targeted therapies, HYRNUO can cause side effects, some of which can be serious. The prescribing information includes warnings for diarrhea, liver problems (hepatotoxicity), lung inflammation (interstitial lung disease/pneumonitis), eye problems, increases in pancreatic enzymes, and potential harm to an unborn baby, so patients should discuss these risks with their oncology team and report new or worsening symptoms right away.
Patients who think they may be candidates for HYRNUO should ask their doctor whether their tumor has been tested for HER2 (ERBB2) TKD activating mutations using an FDA-approved test, and how this new option fits into their overall treatment plan, given prior therapies and other health considerations.
Because this is an accelerated approval, further studies are required to confirm long-term clinical benefit, and the prescribing information includes important safety warnings, including risks of diarrhea, liver problems, lung inflammation (ILD/pneumonitis), eye problems, pancreatic enzyme elevations, and potential harm to an unborn baby.
References
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.
