• Results of clinical trial published in The New England Journal of Medicine indicate that a new HER2-targeted tyrosine kinase inhibitor shows good response in treating advanced NSCLC patients 
• HER2 mutations can drive non-small-cell lung cancer (NSCLC) and like EGFR mutations, are associated with lung cancer in patients that have not smoked that occurs more frequently in Asian populations
• Lung cancer is biologically distinct in Asia compared to the West 

Singapore, 21 October 2025 – A global, multicentre, phase 1/2 clinical trial that included clinician-scientists and researchers from MD Anderson Cancer Centre, Seoul National University and the National Cancer Centre Singapore has indicated positive results in treating advanced HER2-mutant non-small-cell lung cancer (NSCLC) with sevabertinib, an oral HER2-targeted tyrosine kinase inhibitor. Published in The New England Journal of Medicine on 17 October 2025, the findings demonstrate sevabertinib’s potential to be a new precision treatment for this deadly disease.

HER2-mutant lung cancer

Lung cancer is the deadliest cancer worldwide. In Singapore, unlike the West, half of lung cancer patients have never smoked.¹ Many are diagnosed with a form of lung cancer called non-small cell lung cancer (NSCLC), which is often driven by genetic mutations such as EGFR or HER2. HER2 is found in 1-3% of NSCLC cases in the United States and Europe and 1.4-6.7% cases in Asia.² This type of lung cancer is typically treated with platinum-based chemotherapy with or without immunotherapy, but more precision oncology therapies are needed for HER2-mutant NSCLC, as existing targeted therapies used to date have limited efficacy or serious side effects for this group.

A new way to treat HER2 mutant lung cancer

To address this need, a team of oncologists and clinicians conducted the SOHO-01 clinical trial using sevabertinib, an oral HER2-targeted tyrosine kinase inhibitor which works by inhibiting tumours harbouring HER2 mutations. In total 209 patients, enrolled across multiple international sites including Asia (67-70%), Western Europe and Israel (24-33%), and North America (up to 18%), were treated with 20 mg sevabertinib twice daily.

Patients were divided in three cohorts:

• Cohort D: 81 HER2-mutant NSCLC patients who were previously treated but had never had HER2 targeted therapy 
• Cohort E: 55 HER2-mutant NSCLC patients who were previously treated with HER2 antibody-drug conjugates 
• Cohort F: 73 untreated HER2-mutant NSCLC patients 

Patients in Cohort D and F achieved high objective response rates, with tumours shrinking or disappearing, of 64% and 71%, respectively. Cohort E’s response was more moderate with a 38% objective response rate. Median duration of response, or the length of time the cancer was controlled, was 9.2 months, 8.5 months and 11 months for Cohorts D, E and F. Median progression free survival was 8.3 months for Cohort D and 5.5 months for Cohort E while this has not been reached yet for Cohort 5.

Diarrhoea was the most common side effect, and was experienced by 84-91% of patients, but it was mostly low grade and manageable with dose interruptions and/or adjustments. Only 1-5% of patients stopped treatment due to drug-related adverse events.

Implications for patients

The study’s senior author Professor Daniel Tan, Senior Consultant, Division of Medical Oncology, and Head of the Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore said, “In this first in human trial, sevabertinib demonstrated efficacy across all treatment naïve and pre-treated cohorts, and up to 64-71% in patients who have never been treated with HER2-targeted therapy, with responses lasting over 9 months. Importantly, the safety profile was manageable, with most patients able to continue treatment. This gives us great hope in our efforts to improve outcomes for this patient population which has been challenging to treat effectively.”

A phase 3 SOHO-02 trial of sevabertinib as first-line therapy in patients with locally advanced or metastatic HER2-mutant NSCLC is planned. There are also plans to explore sevabertinib efficacy with different types of HER2 mutations, its impact on brain metastases, and potential resistance mechanisms.

¹Toh, C. K., Ong, W. S., Lim, W. T., Tan, D. S., Ng, Q. S., Kanesvaran, R., Seow, W. J., Ang, M. K., & Tan, E. H. (2018). A Decade of Never-smokers Among Lung Cancer Patients-Increasing Trend and Improved Survival. Clinical lung cancer, 19(5), e539–e550. https://doi.org/10.1016/j.cllc.2018.03.013

²Ren, S., Wang, J., Ying, J., Mitsudomi, T., Lee, D. H., Wang, Z., Chu, Q., Mack, P. C., Cheng, Y., Duan, J., Fan, Y., Han, B., Hui, Z., Liu, A., Liu, J., Lu, Y., Ma, Z., Shi, M., Shu, Y., Song, Q., … Hirsch, F. R. (2022). Consensus for HER2 alterations testing in non-small-cell lung cancer. ESMO open, 7(1), 100395. https://doi.org/10.1016/j.esmoop.2022.100395

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Study citation: Le, X., Kim, T. M., Loong, H. H., Prelaj, A., Goh, B. C., Li, L., Fang, Y., Lu, S., Dong, X., Wu, L., Shinno, Y., Daniele, G., Yang, T.-Y., Kim, H. R., Ruiter, G., Zhao, J., Novello, S., Miao, L., Jänne, P. A., Goto, K., Rüttinger, D., Descamps, T., Brase, J. C., Bao, W., Li, R., Brega, N., Grassi, P., Girard, N., & Tan, D. S.-W. (2025). Sevabertinib in advanced HER2-mutant non-small-cell lung cancer. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2511065

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For media enquiries, please contact:

Dharshini Subbiah
National Cancer Centre Singapore
Corporate Communications
Email : dharshini.subbiah@nccs.com.sg 

About the National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre dedicated to advancing cancer care, research and education. With a comprehensive suite of specialties and services, NCCS treats all cancers and offers personalised and multidisciplinary care to ensure that patients receive holistic, compassionate care and support. Advanced and innovative treatments such as proton therapy at the Goh Cheng Liang Proton Therapy Centre, immunotherapy, and cell therapy are available at NCCS to give patients the best treatment outcomes.

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