FDA Grants Breakthrough Status to Sevabertinib in 1L HER2+ NSCLC

The FDA has granted breakthrough therapy designation (BTD) to sevabertinib (Hyrnuo, formerly BAY 2927088) for the first-line treatment of patients with unresectable or metastatic non–small cell lung cancer (NSCLC) harboring activating HER2 (ERBB2) mutations.¹

The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has also granted BTD to the agent for the same indication.

The regulatory decisions, announced by Bayer, signify a shift toward targeted intervention in the treatment-naive setting for a molecular subset of lung cancer that has historically lacked approved frontline targeted therapies.

Sevabertinib is an investigational, oral, highly selective tyrosine kinase inhibitor (TKI) designed to target both HER2 and EGFR mutations, with specific potency against HER2 exon 20 insertions and point mutations.

“The [BTD] granted by the [US] FDA and the CDE in China for sevabertinib as a potential first-line therapy in advanced HER2-mutant NSCLC, further underscore its potential to transform the lives of patients affected by this devastating cancer, which has limited treatment options and poor prognosis," said Christian Rommel, PhD, head of Research and Development at Bayer’s Pharmaceuticals Division, in a news release. “These latest regulatory milestones closely follow the recent accelerated FDA approval for sevabertinib in previously treated advanced HER2-mutant NSCLC and highlight Bayer’s commitment to develop precise and personalized healthcare solutions that address critical unmet needs and help improve outcomes and extend survival for these patients.”

In November 2025, the FDA approved sevabertinib for the treatment of adult patients with previously treated locally advanced or metastatic, nonsquamous NSCLC whose tumors harbor HER2 tyrosine kinase domain mutations.²

Clinical Foundation: The SOHO-01 Study

The BTD is supported by interim evidence from the SOHO-01 study (NCT05099172), an open-label, multicenter phase 1/2 dose-escalation and expansion trial evaluating the safety and efficacy of sevabertinib.^1,3 Data from treatment-naive and pretreated patient cohorts were presented at the 2025 ASCO Annual Meeting.⁴

In treatment-naive patients, after a median follow-up of 5.6 months, the investigator-assessed overall response rate was 59.0% (95% CI, 42.1%–74.4%), which included no complete response, a partial response rate of 59.0%, stable disease rate of 30.8%, and progressive disease rate of 7.7%. The disease control rate was 84.6% (95% CI, 69.5%–94.1%).

At the time of data cutoff, 32 patients (82.1%) were ongoing with sevabertinib treatment. The median duration of treatment was 5.6 months (range, 0.3–6.9).

The safety profile was consistent with those previously reported. Treatment-related grade 3 diarrhea was reported in 1 patient (3%). Overall, no grade 4 diarrhea was reported. In addition, investigators saw no reports of interstitial lung disease or pneumonitis. One patient (2.6%) discontinued treatment as a result of treatment-related adverse events.

“The absence of [interstitial lung disease] is an important distinction of sevabertinib vs trastuzumab deruxtecan [T-DXd; Enhertu], as well as other [TKIs] being used in other therapeutic indications. This may provide us some confidence in the possibility of combination treatment in the future,” said Herbert H F Loong, MBBS(HK), PDipMDPath(HK), MRCP(UK), FRCP Edin, FHKCP, FHKAM(Medicine), FASCO, a clinical associate professor in the Department of Clinical Oncology and the deputy medical director of the Phase 1 Clinical Trials Centre at The Chinese University of Hong Kong, in an interview with Targeted Oncology. Loong presented the data from SOHO-01 at the 2025 ASCO Annual Meeting.

The transition from phase 1/2 success to definitive evidence is currently underway with the SOHO-02 trial (NCT06452277).¹ This global, randomized phase 3 study is comparing sevabertinib against the current standard of care—platinum-based chemotherapy combined with pembrolizumab (Keytruda)—in the first-line setting for patients with advanced HER2-mutant NSCLC.

REFERENCES

1. Bayer receives breakthrough therapy designation in the U.S. and China for sevabertinib as a first-line treatment for patients with HER2-mutant non-small cell lung cancer. News release. Bayer. January 6, 2026. Accessed January 6, 2026. https://tinyurl.com/5hbten53

2. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. US FDA. November 19, 2025. Accessed January 6, 2026. https://tinyurl.com/wyesray4

3. First in human study of BAY2927088 in participants who have advanced non-small cell lung cancer (NSCLC) with mutations in the genes of epidermal growth factor receptor (EGFR) and/​or human epidermal growth factor receptor 2 (HER2). ClinicalTrials.gov. Updated December 15, 2025. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT05099172

4. Loong HH, Li L, Wu L, et al. SOHO-01: Safety and efficacy of BAY 2927088 in patients with advanced HER2-mutant non-small cell lung cancer (NSCLC) who were pretreated but naïve to HER2-targeted therapy or had not received any treatment for advanced disease. J Clin Oncol. 2025;43(16):abstract 8504. doi:10.1200/JCO.2025.43.16_suppl.8504