The U.S. Food and Drug Administration (FDA) has granted accelerated approval to sevabertinib for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors harbor HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.
The decision, announced on September 9, 2026, expands the previous indication for sevabertinib by removing the requirement for prior systemic therapy, extending its use to patients who have not previously received systemic treatment for locally advanced or metastatic disease.
SOHO-01 Trial Supports the Expanded Approval
The latest FDA decision was supported by efficacy findings from SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort clinical trial evaluating sevabertinib in patients with HER2-mutant NSCLC.
HER2 (ERBB2) activating mutations were identified in tumor tissue or plasma by local laboratories before enrollment.
For the population supporting the expanded indication, efficacy was evaluated in 69 patients with locally advanced or metastatic non-squamous NSCLC harboring HER2 (ERBB2) TKD activating mutations who had not received prior systemic therapy.
The study’s major efficacy endpoints were confirmed objective response rate (ORR) and duration of response (DOR), assessed by blinded independent central review using RECIST v1.1.
Objective Response Rate Reached 75%
Among the 69 previously untreated patients, sevabertinib demonstrated a confirmed ORR of 75% (95% CI, 64%–85%).
Among patients who responded:
- 73% maintained a response for at least 6 months;
- 38% maintained a response for at least 12 months.
The FDA approval page does not report a median duration of response for this previously untreated cohort.
Previous FDA Approval of Sevabertinib
Sevabertinib first received FDA accelerated approval on November 19, 2025, for adults with locally advanced or metastatic non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations who had already received systemic therapy.
That initial approval was also based on results from SOHO-01.
Among 70 patients who had received prior systemic therapy but were naïve to therapies specifically targeting HER2 mutations, the confirmed ORR was 71% (95% CI, 59%–82%). Median DOR was 9.2 months (95% CI, 6.3–15.0), and 54% of responders maintained their response for at least 6 months.
A separate cohort included 52 patients who had received prior systemic therapy, including a HER2-targeted antibody-drug conjugate. In this group, the ORR was 38% (95% CI, 25%–53%), median DOR was 7.0 months (95% CI, 5.6–not evaluable), and 60% of responders had a response lasting at least 6 months.
The September 2026 decision therefore expands the regulatory indication beyond the previously treated population to include patients with HER2-mutant locally advanced or metastatic non-squamous NSCLC regardless of prior systemic treatment.
Safety and Recommended Dose
According to the FDA, the prescribing information for sevabertinib includes warnings and precautions for:
- diarrhea;
- hepatotoxicity;
- interstitial lung disease (ILD)/pneumonitis;
- left ventricular dysfunction;
- ocular toxicity;
- pancreatic enzyme elevation;
- embryo-fetal toxicity.
The recommended dose of sevabertinib is 20 mg orally twice daily with food, continued until disease progression or unacceptable toxicity.
Accelerated Approval and Confirmatory Trial
The indication was granted through the FDA’s accelerated approval pathway. The FDA lists an ongoing confirmatory requirement for SOHO-02 (NCT06452277), a Phase 3 randomized trial designed to verify and further characterize the clinical benefit of sevabertinib in patients with previously untreated, locally advanced or metastatic HER2-mutant NSCLC.
SOHO-02 is an open-label, randomized, active-controlled, multicenter study comparing sevabertinib with standard-of-care treatment. According to the ClinicalTrials.gov record, the trial has an estimated enrollment of 444 participants and compares sevabertinib with a standard-of-care regimen consisting of pembrolizumab plus platinum-based chemotherapy.
The FDA lists October 31, 2029 as the originally projected completion date for the accelerated approval post-marketing requirement.
FDA Review and Expedited Programs
The application was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent review of oncology products among international regulatory authorities.
For the latest indication expansion, the FDA collaborated with the UK Medicines and Healthcare products Regulatory Agency (MHRA). Reviews by other participating regulatory agencies are ongoing.
The application was granted Priority Review, while sevabertinib had also received Breakthrough Therapy designation and Orphan Drug designation.
The September 2026 decision marks the second FDA accelerated approval involving sevabertinib in HER2-mutant NSCLC and broadens its indication to include patients who have not previously received systemic therapy for advanced disease.
Read further on OncoDaily: Japan Approves Bayer’s Sevabertinib for HER2-Mutant NSCLC Across All Lines of Therapy
