Sevabertinib approved in the US for untreated HER2-mutant NSCLC

A 75% response rate in 69 patients who had received no prior treatment

The efficacy population was 69 patients from cohort F of SOHO-01, all with locally advanced or metastatic non-squamous non-small cell lung cancer and a HER2 tyrosine kinase domain mutation, and none treated systemically for advanced disease. The confirmed objective response rate was 75%, with a 95% confidence interval of 64% to 85%. Four patients (6%) had a complete response and 48 (70%) a partial response.

SOHO-01 has no control arm. The trial is open-label, single-arm and multi-cohort, so the response rate records what happened to patients given sevabertinib and carries no internal comparison with pembrolizumab plus platinum-based chemotherapy, which is the regimen most of these patients would otherwise have started. Sixty-nine patients is also a small base for an interval: the lower bound of 64% is the figure that survives the uncertainty.

Four complete responses, and no median duration of response reported

Durability was reported as two proportions rather than as a median. Of the patients who responded, 73% were still in response at six months and 38% at 12 months. The FDA’s approval notice gives no median duration of response, no median follow-up time and no progression-free or overall survival figures for the cohort.

Those medians do exist for a larger cutoff of the same cohort: the Japanese approval, granted a fortnight earlier on 73 patients, reported a median duration of response of 12.2 months and a median progression-free survival of 13.5 months. The absence of a median follow-up time on the American notice is what limits reading its two landmark proportions, because a 12-month figure is interpreted differently depending on how many patients had been observed that long at the cutoff.

Diarrhoea in 90% and rash in 76%, with serious adverse reactions in a third

The safety figures come from the whole SOHO-01 safety population of 191 patients rather than from cohort F alone. The adverse reactions reported in more than 20% of those patients were diarrhoea (90%), rash (76%), stomatitis (37%), paronychia (36%), nausea (22%) and weight decrease (22%). Serious adverse reactions occurred in 33%; those reported in at least 2% were diarrhoea (3.7%), vomiting (3.7%), dyspnoea (3.1%), pneumonia (2.6%) and pleural effusion (2.1%).

The label carries warnings and precautions for diarrhoea, hepatotoxicity, interstitial lung disease and pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation and embryo-fetal toxicity. The recommended dose is 20 mg orally twice daily with food, continued until disease progression or unacceptable toxicity.

“The FDA’s accelerated approval of HYRNUO marks an important advance for treatment-naïve patients with HER2-mutated NSCLC. This milestone also underscores the critical importance of comprehensive molecular testing at diagnosis, including for activating HER2 mutations, to ensure patients receive the most appropriate treatment as early as possible.”Xiuning Le, Associate Professor of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, and SOHO-01 lead investigator

How the first-line figures compare with the two previously treated cohorts

Sevabertinib was first approved on 19 November 2025 for patients who had already received systemic therapy, on two other SOHO-01 cohorts. Cohort D, comprising 70 patients with prior systemic therapy but no prior HER2-directed agent, had an objective response rate of 71% (95% CI 59–82) and a median duration of response of 9.2 months (95% CI 6.3–15.0). Cohort E, comprising 52 patients whose prior therapy had included a HER2-targeted antibody-drug conjugate, had a response rate of 38% (95% CI 25–53) and a median duration of response of 7.0 months.

Read together, the three cohorts separate along prior HER2 exposure rather than along treatment line: response rates of 75% and 71% in HER2-naive disease, treated and untreated, against 38% after an antibody-drug conjugate. That pattern is descriptive, since the cohorts were enrolled separately and were never randomised against each other.

Accelerated approval that SOHO-02 must confirm, with its primary readout due in 2027

The approval was granted under the accelerated pathway on Priority Review, with sevabertinib holding Breakthrough Therapy and Orphan Drug designations, and was reviewed under Project Orbis alongside the United Kingdom’s Medicines and Healthcare products Regulatory Agency. Continued approval is contingent on confirmation of clinical benefit in SOHO-02, a randomised phase 3 trial of 444 treatment-naive patients comparing sevabertinib with pembrolizumab plus platinum-based chemotherapy. Its registry record, last updated on 10 September 2026, gives an estimated primary completion of 28 October 2027 and an estimated study completion of 27 June 2029.

Japan reached the same position first. The Ministry of Health, Labour and Welfare approved sevabertinib on 24 August 2026 for HER2 mutation-positive unresectable advanced or recurrent disease with no restriction on line of therapy, 16 days before the American decision.