FDA Clears Hyrnuo for First-Line HER2-Mutant Lung Cancer

FDA granted accelerated approval on 9 September to sevabertinib (Hyrnuo, Bayer) as a first-line, untreated option for adults with locally advanced or metastatic non-squamous non-small cell lung cancer carrying HER2 (ERBB2) tyrosine kinase domain activating mutations. The drug already had accelerated approval for the same mutation in previously treated patients, cleared in November 2025. The new action removes the prior-therapy requirement, on the strength of a 75% response rate in patients who had never received systemic treatment.

A narrower drug gets a wider door

Sevabertinib is a kinase inhibitor built around a specific molecular target: activating mutations in the tyrosine kinase domain of HER2 (ERBB2), found in a minority of non-squamous NSCLC tumors. When FDA first cleared the drug in November 2025, the indication was deliberately narrow — it applied only to patients whose disease had already progressed on another systemic therapy, the standard entry point for an accelerated approval built on single-arm response data in a previously treated population.

The 9 September action removes that entry requirement. Hyrnuo is now approved as a first-line option, meaning oncologists can prescribe it to newly diagnosed patients with a confirmed HER2 TKD mutation before trying anything else. That is a meaningfully different claim: it says the drug's benefit-risk profile holds up not just as a later-line rescue option, but as an opening move against a genomically defined subset of lung cancer.

The data behind the expansion

FDA's decision rests on SOHO-01 (NCT05099172), an ongoing Phase 1/2, open-label, single-arm, multicenter trial organized into cohorts by treatment history. The efficacy population for this expansion was Cohort F: 69 patients with locally advanced or metastatic non-squamous NSCLC and a confirmed HER2 TKD activating mutation who had not received any prior systemic therapy for their disease, identified using an FDA-authorized test.

• Objective response rate: 75% (95% CI, 64%–85%) among the 69 treatment-naïve patients.
• Durability: among responders, 73% had a response lasting at least six months, and 38% had one lasting at least a year.
• Dosing: 20 mg orally, twice daily, with food, continued until disease progression or unacceptable toxicity.
• Companion diagnostic: FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) to identify eligible patients.

What the accelerated pathway still owes

Response rate and duration of response are surrogate measures, not proof that patients live longer or better — which is precisely why this is an accelerated approval rather than a standard one. Continued marketing of Hyrnuo in this first-line population is contingent on verification of clinical benefit in a confirmatory trial; if that trial fails to confirm benefit, FDA can withdraw the indication. For regulatory affairs teams tracking the product, the confirmatory-trial obligation is now the operative deadline, not the approval date.

Safety label carries several boxed precautions

The prescribing information lists warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD) and pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. ILD/pneumonitis occurred in 1.4% of the pooled safety population, including 0.3% at Grade 3; patients are to be monitored for new or worsening dyspnea, cough, or fever, and the drug discontinued if ILD/pneumonitis is confirmed. Diarrhea is the most common adverse reaction reported above 20% incidence, and the label instructs patients to begin antidiarrheal treatment and increase fluid intake at the first sign of it, contacting their prescriber immediately.