How Sevabertinib Stacks Up Against Other HER2-Directed NSCLC Options

Sevabertinib (Hyrnuo) is an oral HER2 tyrosine kinase inhibitor (TKI) with FDA accelerated approval for frontline use in HER2-mutant non–small cell lung cancer (NSCLC). Previously, zongertinib (Hernexeos) received frontline accelerated approval in February 2026 based on the phase 1b Beamion LUNG-1 trial (NCT04886804).^1,2 Trastuzumab deruxtecan (Enhertu), an antibody-drug conjugate, is also an option in the previously treated setting.

Xiuning Le, MD, PhD, an associate professor in the department of Thoracic/Head and Neck Medical Oncology at UT MD Anderson Cancer Center, spoke with CancerNetwork^® about how she weighs these HER2-directed modalities against one another. She noted her strategy of using an oral TKI like sevabertinib in the frontline setting followed by other targeted approaches. Additionally, she said the field is still in the process of learning how to sequence or combine these modalities to further improve outcomes for patients.

Transcript:

CancerNetwork: There are a lot of HER2-directed options in the lung cancer space right now. How do you weigh these modalities against each other, and does giving one before another make more sense in your view?

The development of anti-HER2 agents in lung cancer has been evolving very fast, which is a fantastic thing for patients and physicians like myself. We now have 2 oral medication TKIs that have received FDA accelerated approval for use in the frontline setting: sevabertinib [and] zongertinib. The other modality we can use in the previously treated patient population is trastuzumab deruxtecan, which is an antibody-drug conjugate, also with very good efficacy.

Now, when I see a [patient with] newly diagnosed HER2 mutation-positive non–small cell lung cancer, I do follow the FDA approval and provide an oral medication TKI, such as sevabertinib, in the first-line setting and then move to other targeted approaches such as trastuzumab deruxtecan. However, we’re still in the learning process of how to sequence, or combine, those drugs to maximize the benefit for each patient.

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 September 21, 2026. https://tinyurl.com/mwsay6jf
2. FDA grants second approval under the National Priority Voucher Pilot Program. News release. FDA. February 26, 2026. Accessed February 26, 2026. https://tinyurl.com/efhx9sr9