Bayer’s Sevabertinib Gains First-Line FDA Approval in HER2-Mutant NSCLC

Bayer announced on September 9, 2026, that the U.S. Food and Drug Administration (FDA) granted accelerated approval to sevabertinib as a first-line treatment option for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. According to the company, the decision follows FDA Priority Review and Breakthrough Therapy Designation for sevabertinib in this setting.

Sevabertinib is an oral, reversible, small molecule tyrosine kinase inhibitor (TKI). Bayer states that the compound potently inhibits mutant HER2, including HER2 exon 20 insertions and HER2 point mutations, by blocking tyrosine kinases involved in the growth of cancer cells, and that reversible TKIs temporarily block their targets, which the company says allows more precise control over treatment and potentially reduces long-term side effects compared with irreversible TKIs. The drug originates from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard.

SOHO-01 Data and the Confirmatory-Trial Condition

The FDA approved the first-line indication under its accelerated approval pathway based on objective response rate (ORR) and duration of response (DOR) in a cohort of 69 treatment-naive patients in the ongoing Phase I/II SOHO-01 trial (NCT05099172), which is evaluating the efficacy and safety of sevabertinib in patients with locally advanced or metastatic HER2-mutant NSCLC. In that cohort, the ORR was 75%, including complete responses in 6% of patients and partial responses in 70%, with 73% of responders maintaining a response for at least six months, Bayer reported. The company said the safety profile of sevabertinib was consistent with previous findings.

Continued approval for the first-line indication may be contingent upon verification and description of clinical benefit in the ongoing Phase III SOHO-02 confirmatory trial (NCT06452277), which is evaluating sevabertinib against standard of care in treatment-naive patients with advanced HER2-mutant NSCLC, Bayer said.

“The FDA’s accelerated approval of sevabertinib marks an important advance for treatment-naïve patients with HER2-mutated NSCLC who historically have a poor prognosis,” said Xiuning Le, MD, PhD, SOHO-01 lead investigator and associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Le added that the milestone underscores the critical importance of comprehensive molecular testing at diagnosis, including for activating HER2 mutations, so that patients receive the most appropriate treatment as early as possible.

Christine Roth, Executive Vice President of Global Product Strategy and Commercialization and a member of Bayer’s Pharmaceuticals Leadership Team, called the approval “a powerful validation of Bayer’s commitment to advancing precision oncology in areas with the highest unmet needs.” Roth said HER2-mutated NSCLC is a distinct subtype that often affects people who have never smoked, and that there remains a critical need for additional treatment options for these patients.

Prior Approvals in the United States, China, and Japan

On November 19, 2025, the FDA granted accelerated approval to sevabertinib (Hyrnuo, Bayer HealthCare Pharmaceuticals Inc.) for adults with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) TKD activating mutations, as detected by an FDA-approved test, and who had received prior systemic therapy, according to the agency’s approval notice. At the same time, the FDA approved the Oncomine Dx Target Test from Life Technologies Corporation as a companion diagnostic to aid in detecting HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for sevabertinib treatment.

The earlier approval was also based on SOHO-01, an open-label, single-arm, multicenter, multi-cohort trial in which the major efficacy outcome measures were confirmed ORR and DOR as assessed by BICR using RECIST v1.1, with HER2 (ERBB2) activating mutations determined in tumor tissue or plasma by local laboratories before enrollment. Among 70 previously treated patients who were naive to HER2-targeted therapy, the FDA reported an ORR of 71% (95% CI: 59, 82), a median DOR of 9.2 months (95% CI: 6.3, 15.0), and 54% of responders maintaining a response for at least six months. Among 52 patients previously treated with HER2-directed antibody-drug conjugates, the ORR was 38% (95% CI: 25, 53), with a median DOR of 7.0 months (95% CI: 5.6, not evaluable) and 60% of responders maintaining a response for at least six months.

In its release, Bayer said the November 2025 approval drew on SOHO-01 cohort D, comprising previously treated patients who had not received HER2-targeted therapy, and cohort E, comprising patients who had previously received HER2-directed antibody-drug conjugates. According to the FDA notice, the prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity, and the recommended dose is 20 mg taken orally twice daily with food until disease progression or unacceptable toxicity.

The November 2025 review was conducted under Project Orbis, an FDA Oncology Center of Excellence initiative that provides a framework for concurrent submission and review of oncology drugs among international partners. For that review, the FDA collaborated with Health Canada, Israel’s Ministry of Health, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency, and the agency said application reviews remained ongoing at the other regulatory agencies. The application was granted priority review, and sevabertinib received breakthrough and orphan drug designations, according to the notice.

Outside the United States, China’s National Medical Products Administration approved sevabertinib earlier in 2026 as monotherapy for adults with unresectable, locally advanced or metastatic NSCLC whose tumors have HER2 activating mutations and who had received one prior systemic therapy, Bayer said. That approval followed a Breakthrough Therapy Designation from China’s Center for Drug Evaluation (CDE) for this patient population, and the CDE has also granted sevabertinib Breakthrough Therapy Designation to expedite its development for first-line use in advanced HER2-mutant NSCLC. In Japan, the Ministry of Health, Labour and Welfare has approved sevabertinib as the first targeted therapy for this indication that can be used regardless of line of therapy, including as a first-line treatment, according to the company.

Beyond SOHO-01 and SOHO-02, sevabertinib is being studied in the panSOHO study (NCT06760819) in patients with metastatic or unresectable solid tumors with HER2-activating mutations, excluding advanced NSCLC.

Lung cancer is the leading cause of cancer-related deaths worldwide, and NSCLC accounts for more than 85% of lung cancer cases, according to Bayer’s release. The company states that activating HER2 mutations are found in 2% to 4% of patients with advanced NSCLC, and that 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes the disease more difficult to treat.