FDA Expands Accelerated Approval of Sevabertinib to First-Line HER2-Mutant NSCLC

The FDA has granted accelerated approval to sevabertinib (Hyrnuo; Bayer HealthCare Pharmaceuticals Inc) for adults with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors harbor activating HER2 (ERBB2) tyrosine kinase domain (TKD) mutations, as detected by an FDA-authorized test.¹

The FDA’s September 9, 2026, decision 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. The expanded indication makes the oral kinase inhibitor available regardless of whether a patient has previously received systemic treatment.^1,2

Continued approval for this indication may depend on the verification and description of clinical benefit in a confirmatory trial.¹

SOHO-01 Supports First-Line Expansion

The FDA’s decision was supported by findings from SOHO-01 (NCT05099172), an ongoing phase 1/2, open-label, single-arm, multicenter, multicohort trial evaluating sevabertinib in patients with advanced NSCLC harboring HER2 or EGFR mutations. HER2-activating mutations were identified in tumor tissue or plasma by local laboratories before enrollment.^1,3

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 1.1.¹

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. These findings provided the response-based evidence supporting accelerated approval in the treatment-naive population.¹

The first-line application previously received a priority review based on preliminary evidence from cohort F of SOHO-01. Sevabertinib also received a breakthrough therapy designation for first-line use in HER2-mutant NSCLC, as well as an orphan drug designation.^1,4

Biomarker Testing Defines Eligibility

The indication reinforces the importance of comprehensive molecular testing before treatment begins. Eligibility is limited to patients with nonsquamous NSCLC whose tumors contain qualifying HER2 TKD–activating mutations detected by an FDA-authorized test.¹

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. Confirming the specific alteration and reviewing the authorized test result are therefore essential before sevabertinib is dispensed.

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.¹

The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. Patients should receive clear guidance about reporting new or worsening respiratory symptoms, vision changes, or persistent gastrointestinal effects.¹

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. Pharmacists can support early recognition of adverse effects and coordinate dose modifications or treatment interruption when clinically indicated.¹

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. For this application, the FDA collaborated with the United Kingdom’s Medicines and Healthcare products Regulatory Agency; reviews at the other participating agencies remain ongoing.^1,5

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.

REFERENCES

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. FDA. September 9, 2026. Accessed September 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small

2. US FDA grants accelerated approval to Bayer’s Hyrnuo (sevabertinib) for patients with previously treated advanced HER2-mutant non-small cell lung cancer. News release. Bayer. November 20, 2025. Accessed September 9, 2026. https://www.bayer.com/media/en-us/us-fda-grants-accelerated-approval-to-bayers-hyrnuo-sevabertinib-for-patients-with-previously-treated-advanced-her2-mutant-non-small-cell-lung-cancer/

3. Study to learn more about the study treatment BAY2927088 in participants with advanced non-small cell lung cancer with specific genetic changes called mutations (SOHO-01). ClinicalTrials.gov. Updated August 28, 2026. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT05099172?term=NCT05099172&rank=1

4. Le X, Kim TM, Loong HH, et al. Sevabertinib in advanced HER2-mutant non-small-cell lung cancer. N Engl J Med. 2025;393(18):1819-1832. doi:10.1056/NEJMoa2511065

5. Project Orbis. FDA. Updated September 18, 2024. Accessed September 9, 2026. https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis