The FDA has granted accelerated approval to sevabertinib (Hyrnuo; Bayer HealthCare Pharmaceuticals Inc.) for adults with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) whose tumors harbor activating HER2 (ERBB2) tyrosine kinase domain (TKD) mutations, as detected by an FDA-authorized test.
The September 9, 2026, decision, announced by the FDA in a news release, expands the indication into the first-line setting. Sevabertinib previously received accelerated approval in November 2025 for adults with the same tumor characteristics who had received prior systemic therapy.
Continued approval for this indication may depend on verification and description of clinical benefit in a confirmatory trial.
SOHO-01 Supports First-Line Expansion
The decision was supported by findings from SOHO-01 (NCT05099172), an ongoing phase 1/2, open-label, single-arm, multicenter, multi-cohort trial evaluating sevabertinib in patients with advanced NSCLC harboring HER2 or EGFR mutations.
The efficacy population for the expanded indication included 69 patients with locally advanced or metastatic NSCLC harboring HER2 TKD activating mutations who had not received prior systemic therapy. The major efficacy end points were confirmed objective response rate (ORR) and duration of response (DOR), assessed by blinded independent central review according to RECIST version 1.1.
Sevabertinib produced an ORR of 75% (95% CI, 64%-85%). Among patients who responded, 73% maintained a response for at least 6 months and 38% maintained a response for at least 12 months.
Biomarker Testing Defines Eligibility
The indication reinforces the importance of molecular testing before treatment begins. Eligibility is limited to patients with non-squamous NSCLC whose tumors contain qualifying HER2 TKD activating mutations detected by an FDA-authorized test.
HER2 mutation should not be conflated with HER2 protein overexpression or gene amplification. These biomarkers describe different forms of HER2 alteration and do not automatically establish eligibility for a mutation-directed therapy.
For oncology pharmacists, the expansion may move sevabertinib counseling and medication-management responsibilities earlier in the treatment course. Pharmacists can help verify the molecular result, review the medication list for potential management concerns, reinforce administration instructions, and establish a plan for toxicity monitoring.
Dosing and Safety Considerations
The recommended sevabertinib dosage is 20 mg orally twice daily with food. Treatment should continue until disease progression or unacceptable toxicity.
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
Monitoring should reflect the toxicities described in the prescribing information, including assessment of hepatic function and pancreatic enzymes. Evaluation of cardiac function may also be required.
Approval Conducted Through Project Orbis
The FDA conducted the review through Project Orbis, an Oncology Center of Excellence initiative that provides a framework for concurrent oncology product submissions and reviews among international regulatory partners.
The first-line expansion establishes sevabertinib as an additional biomarker-directed option for HER2 TKD–mutated advanced NSCLC. Its use will depend on accurate molecular identification, appropriate patient selection, and proactive toxicity management throughout treatment.
Given the specific nature of HER2 mutations and their impact on treatment outcomes, targeted therapies like sevabertinib are becoming increasingly important in the treatment of NSCLC. As research continues to uncover the complexities of HER2 mutations, further developments in this area are likely, with potential benefits for patients with this type of cancer.
The FDA’s decision to grant accelerated approval to sevabertinib for first-line treatment of HER2-mutant NSCLC highlights the ongoing efforts to provide patients with access to effective treatments for this disease. As the treatment environment evolves, it is essential to stay informed about the latest developments and advancements in this field.
Bayer HealthCare Pharmaceuticals Inc. will continue to play a role in the development and distribution of sevabertinib.
The FDA’s approval process involves careful evaluation of clinical trial data.
Sevabertinib has shown promise in clinical trials.
Patients with HER2-mutant NSCLC may benefit from this new treatment option.
The medical community will continue to monitor the effectiveness of sevabertinib in the treatment of NSCLC.
Additionally, the SOHO-01 trial’s design as a multi-cohort study allows for the evaluation of sevabertinib in different patient populations, including those with EGFR mutations, which may provide valuable insights into the treatment of other types of NSCLC.
