SOHO-01: Updated safety and efficacy of sevabertinib in patients with advanced <i>HER2</i> -mutant non-small cell lung cancer (NSCLC).

Abstract

8622 Background: Sevabertinib, a potent, reversible, oral tyrosine kinase inhibitor, received FDA accelerated approval for pretreated patients with advanced NSCLC harboring HER2 tyrosine kinase domain-activating mutations. Sevabertinib demonstrated significant antitumor activity and manageable safety in patients with HER2 -mutant NSCLC who had previously received treatment (Cohort D) or were treatment-naïve (Cohort F) in the ongoing, open-label, multicenter, Phase I/II SOHO-01 trial (NCT05099172) (Le X et al. N Engl J Med 2025). Here, we report updated safety and efficacy data from Cohorts D and F. Methods: Patients with HER2 -mutant NSCLC received sevabertinib 20 mg twice daily in both cohorts: patients previously treated with systemic therapy but naïve to HER2-targeted therapy (Cohort D) and treatment-naïve patients (Cohort F). The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR) per RECIST v1.1. Other key prespecified and secondary endpoints included duration of response (DoR) and progression-free survival (PFS) assessed by BICR per RECIST v1.1, and safety per MedDRA v28.0 and CTCAE v5.0. Results: In total, 154 patients (n=81, D; n=73, F) received sevabertinib in the two cohorts; median follow-up was 19.5 (D) and 15.0 (F) months. Median age was 60 (D) and 65 (F) years; 61.7% (D) and 63.0% (F) were female; 61.7% (D) and 78.1% (F) had never smoked. As of November 17, 2025, ORR (95% CI) was 66.7% (55.3, 76.8; D) and 75.3% (63.9, 84.7; F); disease control rate (confirmed response or stable disease for ≥12 weeks; 95% CI) was 81.5% (71.3, 89.2; D) and 89.0% (79.5, 95.1; F). Median (95% CI) DoR was 9.5 (6.3, 13.5; D) and 12.2 (8.8, not estimable; F) months; median (95% CI) PFS was 8.3 (6.9, 12.3; D) and 13.5 (10.0, not estimable; F) months. Treatment-related adverse events (TRAEs) in both cohorts were consistent with previous reports. Grade 3 or higher TRAEs occurred in 39.5% (D) and 24.7% (F) of patients. Diarrhea was reported in 86.4% (D) and 87.7% (F) of patients; grade 3 diarrhea occurred in 23.5% (D) and 5.5% (F) of patients. No cases of interstitial lung disease or grade 4 diarrhea, discontinuations due to diarrhea, or new safety signals were observed. Conclusions: Sevabertinib demonstrated sustained efficacy with a manageable safety profile in treatment-naïve and pretreated patients with advanced HER2 -mutant NSCLC. These data further support the rapid and durable responses of sevabertinib for patients with HER2 -mutant NSCLC. Clinical trial information: NCT05099172 .