BAY 2927088 Shows ‘Durable Responses’ in Patients With Previously Treated HER2-Positive NSCLC

BAY 2927088 showed “durable responses” in patients with previously treated HER2-mutated non-small cell lung cancer (NSCLC), according to SOHO-01 study results presented at the European Lung Cancer Congress 2025.

Nicolas Girard, MD, PhD, of Institut Curie, presented the findings from two expansion cohorts of the ongoing, multicenter phase 1/2 study during the first proffered paper session of the congress.

According to the study investigators, BAY 2927088, a potent, oral, reversible HER2 tyrosine kinase inhibitor, previously showed “manageable safety and anti-tumor activity” in patients with advanced NSCLC with HER2-activating mutations.

The study includes patients with advanced NSCLC with HER2-activating mutations who had disease progression after at least one systemic therapy. Cohort D included patients (n=44) who were naïve to HER2-targeted therapy, while cohort E included those who had previously received HER2-targeted antibody-drug conjugates (n=34). The median ages were similar (62 years and 62.5 years) in cohorts D and E, with similar proportions of female patients (63.6% versus 61.8%).

Among patients in cohort D, 70.5% had never smoked, compared with 64.7% in cohort E. More than half (54.5%) of patients in cohort D received at least two lines of therapy, compared with 76.5% of those in cohort E. In cohort E, most patients (82.4%) had received trastuzumab deruxtecan. Both cohorts received oral BAY 2927088 20 mg twice daily in the study, and all were included in the safety and efficacy analysis.

Treatment-related adverse events (TRAEs) were reported in nearly all (97.4%) patients, with diarrhea being the most common TRAE leading to dose reduction. However, none of the patients discontinued treatment due to diarrhea. No cases of interstitial lung disease were reported.

The investigator-assessed objective response rate was 70.5% (95% CI, 54.8 to 83.2) in cohort Dm, nearly double the rate of 35.3% (95% CI, 19.7 to 53.5) reported in cohort E. Cohort D also showed a higher disease control rate, which was defined as a response or stable disease for at least 12 weeks, at 81.8%, compared to 52.9% in cohort E. The median duration of response was 8.7 months (95% CI, 4.5 to not estimable [NE]) in cohort D and 9.5 months (95% CI, 4.1 to NE) in cohort E.

Based on these findings, the study investigators concluded that the safety profile of BAY 2927088 “was manageable across cohorts” and that treatment “led to durable responses” in patients who were naïve to HER2-targeted therapy and in those who had received a HER2-targeted antibody-drug conjugate.

Reference

Girard N, Loong HHF, Boon-Cher Goh BC, et al. Phase I/II SOHO-01 study of BAY 2927088 in patients with previously treated HER2-mutant NSCLC: Safety and efficacy results from 2 expansion cohorts. Abstract #3O. Presented at the European Lung Cancer Congress 2025, March 26-29, 2025; Paris, France.

In the photo at top, Nicolas Girard, MD, PhD, of Institut Curie, presents the findings from two expansion cohorts of the ongoing, multicenter phase 1/2 study during the first proffered paper session of the European Lung Cancer Congress 2025 in Paris, France. (Photo courtesy of the European Society for Medical Oncology)