Dr Le on Early Efficacy Data With Sevabertinib Monotherapy in HER2-Mutant NSCLC

"In the clinical part, we were able to show very good response rate [with sevabertinib] regardless of prior lines of therapy. Overall, we think that this agent is very promising as a new option for patients with HER2-mutant lung cancer."

Xiuning Le, MD, PhD, associate professor in the Department of Thoracic/Head and Neck Medical Oncology of the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center, discussed findings from the phase 1/2 SOHO-01 trial (NCT05099172) evaluating sevabertinib monotherapy for patients with HER2-mutant advanced non–small cell lung cancer (NSCLC).

Le noted that sevabertinib is an oral, irreversible small molecule inhibitor for HER2 that has exhibited high potency against HER2 insertions and kinase mutations. This potency provides strong preclinical evidence supporting its clinical use.

Results from the phase 1/2 trial, which were simultaneously presented during the 2025 ESMO Congress and published in the New England Journal of Medicine, showed that sevabertinib monotherapy elicited robust and durable responses across both frontline and previously treated settings. In cohort D (n = 81), which included patients who were previously treated, the objective response rate (ORR) determined by blinded independent central review was 64% (95% CI, 53%-75%). This included a 2% complete response rate and 62% partial response rate. The disease control rate for this cohort was 81% (95% CI, 71%-89%). In cohort F, which included treatment-naive patients (n = 73), the ORR was 71% (95% CI, 59%-81%).

Subgroup analyses indicated that the ORR remained consistent across all evaluated subgroups, including those based on age, sex, race, number of previous systemic treatments, and the presence of baseline brain metastases, as well as prior receipt of platinum chemotherapies. Le remarked that the response rates with sevabertinib were very good regardless of prior lines of therapy, although the best response was seen in treatment-naive patients. She concluded that the data are very encouraging and positions sevabertinib as a very promising new therapeutic option for patients with HER2-mutant lung cancer.

Disclosures: Dr. Le cited consultant roles for AbbVie, AstraZeneca, BlossomHill, Blueprint Medicines Corporation, Boehringer Ingelheim, Daiichi Sankyo Company, Eli Lilly and Company, Janssen Biotech, Merck KGaA, Novartis, Regeneron Pharmaceuticals, and Spectrum Pharmaceuticals.

References

Le X, Kim TM, Dong X, et al. Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): results from the SOHO-01 study. Presented at the 2025 European Society for Medical Oncology Congress. Presented at the 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA75.