A new anti cancer drug sevabertinib, that targets mutated HER2, has proved effective in the SOHO-01 study among patients wiith HER2 mutated non small cell lung cancer. It has now been reported in the
An interview with: Xiuning Le MD PhD, Medical Oncologist, Department of Thoracic Medicine, UT MD Anderson Cancer Center, Houston TX
BERLIN, Germany—Mutations in the HER2 molecule can be found in a few per cent of non-small cell lung cancers, and these can now be targeted by the new drug sevabertinib that can bring benefit to patients who have the mutation. That’s according to findings from the SOHO-01 study reported at the 2025 Annual Congress of the European Society of Clinical Oncology.
After her talk at the congress, first author Xiuning Le MD PhD, who is a medical oncologist in the Department of Thoracic Medicine, at the University of Texas MD Anderson Cancer Center, in Houston, talked about the new data with Audio Journal of Oncology reporter Peter Goodwin:
Audio Journal of Oncology; Xiuning Le MD PhD
IN: “[GOODWIN] I am at the European Society for Medical ….OUT: ……. For the Audio Journal of Oncology, I’m Peter Goodwin” 10: 18secs
2025 ESMO Berlin ABSTRACT LBA75:
Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study
Speaker: Xiuning Le (Houston, United States of America)
Authors: Xiuning Le (Houston, United States of America) Tae Min Kim (Seoul, Republic of Korea) Xiaorong Dong (Wuhan, China) Herbert Ho Fung Loong (Hong Kong, Hong Kong SAR, China) Nicolas Girard (Paris, France) Shun Lu (Shanghai, China) Hye Ryun Kim (Seoul, Republic of Korea) Boon-Cher Goh (Singapore, Singapore) Arsela Prelaj (Milan, Italy) Yong Fang (Hangzhou, China) Lin Wu (Changsha, China) Yuki Shinno (Tokyo, Japan) Gennaro Daniele (Rome, Italy) Tsung-Ying Yang (Taichung City, Taiwan) Gerrina Ruiter (Amsterdam, Netherlands) Jun Zhao (Beijing, China) Jan Christoph Brase (Basel, Switzerland) Rui Li (Whippany, United States of America) Paolo Grassi (Milan, Italy) Lin Li (Beijing, China)
Background
Sevabertinib is a potent, reversible, oral HER2 tyrosine kinase inhibitor with FDA Breakthrough Therapy Designation and Priority Review for pretreated patients (pts) with advanced HER2-mutant NSCLC. We report updated efficacy and safety in pretreated and treatment-naïve pts with HER2-mutant NSCLC in the open-label, multicenter Phase I/II SOHO-01 study.
Methods
Pts with HER2-mutant NSCLC were treated with sevabertinib 20 mg twice daily in 3 cohorts: Cohort D, previous systemic therapy but naïve to HER2 ex20ins-targeted therapy; Cohort E, previous HER2-targeted antibody-drug conjugates; Cohort F, naïve to systemic anti-cancer therapy for advanced disease. The primary endpoint was objective response rate (ORR) by RECIST v1.1 and blinded independent central review. Secondary endpoints were duration of response (DoR) and progression-free survival (PFS).
Results
At the data cut-off (June 27, 2025), 209 pts with HER2-mutant NSCLC were treated: 81 (D), 55 (E), and 73 (F). ORR (95% CI) was 64% (53, 75; D), 38% (25, 52; E), and 71% (59, 81; F). Median (95% CI) DoR was 9.2 (6.3, 13.5; D), 8.5 (5.6, 16.4; E), and 11.0 (8.1, not evaluable; F) months; 12-month DoR rates (95% CI) were 42% (27, 57; D) and 29% (5, 53; E). Median PFS (95% CI) was 8.3 (6.9, 12.3; D) and 5.5 (4.3, 8.3; E) months, and not reached (F). In Cohort D, pts with baseline brain metastases had a similar ORR to those without (61% vs 65%). Among pts with HER2 tyrosine kinase domain (TKD) mutations, those with Y772_A775dupYVMA had a higher ORR (78% vs 57%) and median PFS (12.2 vs 7.0 months) than those with other HER2 TKD mutations. Overall, grade ≥3 treatment-related adverse events (TRAEs) were reported in 31% of pts. Diarrhea was the most commonly reported TRAE, mostly grade 1/2 (grade 3: 14%). TRAEs led to treatment discontinuation in 3% of pts; none due to diarrhea. There were no reports of interstitial lung disease or pneumonitis.
Conclusions
Sevabertinib showed rapid and durable responses with a manageable safety profile in pretreated and treatment-naïve pts with advanced HER2-mutant NSCLC. These data support sevabertinib as a potential practice-changing, new targeted therapy for pts with HER2-mutant NSCLC.
Clinical trial identification: NCT05099172, March 28, 2025.
Editorial acknowledgement: Alice Xue, MSc, Erica Sedgwick, MSc, and Rachel Fairbanks, BA, of Caudex, IPG Health Medical Communications, provided medical writing and editorial assistance in the development of this abstract, funded by Bayer AG.
Legal entity responsible for the study: Bayer AG.
New England Journal of Medicine
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