What Does Sevabertinib’s Expanded Approval Mean for HER2+ NSCLC?

In September 2026, the FDA granted accelerated approval to sevabertinib (Hyrnuo) as a frontline treatment option for patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD)–activating mutations.¹ The decision expanded sevabertinib’s indication from its accelerated approval in November 2025 as a therapy for patients who received prior systemic treatment.²

To better understand the potential clinical implications of this expanded approval for sevabertinib, CancerNetwork® spoke with Xiuning Le, MD, PhD, about the findings supporting the agent’s clinical benefit and how it fits alongside other available options in the NSCLC space. Le, an associate professor in the department of Thoracic/Head and Neck Medical Oncology at UT MD Anderson Cancer Center, was the lead investigator of the phase 1/2 SOHO-01 trial (NCT05099172), which led to both of sevabertinib’s accelerated approvals.

Regarding sevabertinib’s label, Le highlighted the importance of mindfully interpreting the differences between TKD-activating mutations or insertions vs amplification, as precision oncology begins with the careful testing, detection, and interpretation of patient reports. She also described how the approval supplements the rapid evolution of HER2-directed therapy in lung cancer, as sevabertinib is now an option to consider alongside zongertinib (Hernexeos) and trastuzumab deruxtecan (Enhertu) across different treatment settings.

Given sevabertinib’s accelerated approval status, Le outlined the next steps for affirming the agent’s benefit in the phase 3 SOHO-02 trial (NCT06452277), which is randomly assigning patients with treatment-naive, HER2 mutation-positive NSCLC to receive sevabertinib or chemoimmunotherapy.³ Le concluded by emphasizing the value of testing and identifying patients with actionable markers who may benefit from treatment with sevabertinib and other targeted agents.

“What I want to tell my peer oncologists is that HER2 is still a very new target. Make sure that you sequence all the [patients with] lung cancer to identify the HER2 mutation, as we're all learning how to use these medications,” Le said. “The first, most important part is to identify those patients. Once we identify those patients, then we can discuss which frontline [option] is the most appropriate. Testing still is the key.”

References

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. News release. FDA. September 9, 2026. Accessed October 2, 2026. https://tinyurl.com/mwsay6jf
2. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. FDA. November 19, 2025. Accessed October 2, 2026. https://tinyurl.com/mt455knh
3. A study to learn more about how well sevabertinib works and how safe it is compared with standard treatment, in participants who have advanced non-small cell lung cancer (NSCLC) with mutations of the human epidermal growth factor receptor 2 (HER2) (SOHO-02). ClinicalTrials.gov. Updated September 23, 2026. Accessed October 2, 2026. https://tinyurl.com/2k32z6wu