FDA grants accelerated approval to sevabertinib for untreated HER2-mutant lung cancer

The FDA granted accelerated approval to Bayer Healthcare Pharmaceuticals’ Hyrnuo (sevabertinib) for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors carry HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, regardless of whether they have received prior treatment, the agency hared in an announcement yesterday.

The approval expands sevabertinib's original accelerated approval, which was limited to patients who had already received systemic therapy.

NSCLC makes up about 80% to 85% of lung cancer diagnoses, according to the American Cancer Society, and HER2 mutations occur in roughly 2% to 4% of those cases. Sevabertinib is an oral tyrosine kinase inhibitor designed to reversibly block HER2 signaling, giving patients with this mutation subtype a targeted option beyond chemotherapy or immunotherapy.

Similar to sevabertinib's original approval in November 2025, this expanded indication comes through the FDA's accelerated approval pathway, which allows the agency to clear a cancer drug based on an early measure of benefit, such as tumor response rate, rather than waiting for proof that patients live longer or feel better.

Continued approval for the first-line use may depend on the ongoing phase 3 SOHO-02 trial, which is comparing sevabertinib against standard-of-care therapy in treatment-naive patients with advanced HER2-mutant NSCLC, according to Bayer.

The expanded approval is based on results from SOHO-01, an open-label, single-arm, multicenter, multicohort trial that is testing sevabertinib in patients with HER2-mutant NSCLC. Out of 69 previously untreated patients whose HER2 (ERBB2) TKD mutations were confirmed by an FDA-authorized test, sevabertinib produced a confirmed objective response rate of 75% as assessed by blinded independent central review using RECIST 1.1. This tool measures how well a solid tumor responds to cancer treatment. Among patients who responded, 73% had a response lasting at least six months and 38% had a response lasting at least a year.

That efficacy population is close to, though not identical to, the previously untreated cohort described when SOHO-01's results were first published in the New England Journal of Medicine. That October 2025 publication reported findings from 209 patients enrolled across three cohorts as of a June 2025 data cutoff. Response rates were 64% among 81 previously treated patients who had not had HER2-targeted therapy, 38% among 55 patients who had already received a HER2-directed antibody-drug conjugate and 71% among 73 treatment-naive patients. Median progression-free survival was 8.3 months in the previously treated cohort and 5.5 months in the antibody-drug conjugate-experienced cohort. Progression-free survival data in the treatment-naive cohort were still immature at that data cutoff.

Diarrhea was the trial's most frequently reported side effect, occurring in 84% to 91% of patients across cohorts, with grade 3 or higher diarrhea in 5% to 23%. Grade 3 or higher drug-related adverse events overall occurred in 31% of patients, and 3% of patients discontinued treatment because of drug-related side effects. Sevabertinib's prescribing information also carries warnings for hepatotoxicity, interstitial lung disease and pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation and embryo-fetal toxicity.

The recommended dose is 20 mg taken orally twice daily with food, continued until disease progression or unacceptable toxicity. Full prescribing information will be posted on Drugs@FDA.

Sevabertinib enters a HER2-mutant NSCLC treatment landscape that has built out quickly in recent years. Trastuzumab deruxtecan (Enhertu, Daiichi Sankyo and AstraZeneca) became the first HER2-directed therapy approved for this population in August 2022, though it is an intravenously infused antibody-drug conjugate rather than a pill, according to the FDA. Boehringer Ingelheim's zongertinib (Hernexeos), an oral HER2 tyrosine kinase inhibitor, followed with accelerated approval for previously treated patients in August 2025 and was expanded to treatment-naive patients in February 2026. Sevabertinib's newly broadened approval puts it in direct competition with zongertinib for first-line HER2-mutant NSCLC patients, giving prescribers a second oral targeted option in that setting.

The FDA reviewed the application under Project Orbis, an Oncology Center of Excellence initiative that allows the agency to evaluate oncology drugs alongside international regulators at the same time. For this review, the FDA worked with the United Kingdom's Medicines and Healthcare products Regulatory Agency, and reviews are still underway at other participating agencies. The review also used the FDA's Assessment Aid, a voluntary submission format meant to streamline the agency's evaluation.

"Sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC," the study's authors wrote in the New England Journal of Medicine, noting that diarrhea was the most common adverse event.