SOHO-01: Safety and efficacy of BAY 2927088 in patients with advanced <i>HER2</i> -mutant non-small cell lung cancer (NSCLC) who were pretreated but naïve to HER2-targeted therapy or had not received any treatment for advanced disease.

Abstract

8504 Background: The potent, reversible HER2 tyrosine kinase inhibitor BAY 2927088 has demonstrated manageable safety and anti-tumor activity in patients with advanced NSCLC with HER2 -activating mutations. Here we report safety and efficacy data from 2 cohorts of the ongoing, open-label, multicenter Phase I/II SOHO-01 trial. Methods: Patients with advanced NSCLC with HER2 -activating mutations were enrolled and received oral BAY 2927088 20 mg twice daily. Patients in expansion/extension Cohort D had disease progression following ≥1 systemic therapies and were naïve to HER2-targeted therapy; patients in expansion Cohort F had not received any systemic therapy for locally advanced or metastatic disease. Safety (MedDRA v27.1 and CTCAE v5.0) was the primary endpoint; anti-tumor activity (RECIST v1.1) was a key secondary endpoint. Results: As of October 14, 2024, 81 (D) and 39 (F) patients were treated. Median age was 60 years (D) and 65 years (F), 61.7% (D) and 64.1% (F) were female, 61.7% (D) and 79.5% (F) had never smoked, and 43.2% (D) had received ≥2 systemic therapies. All patients were analyzed for safety and efficacy; response was based on the full analysis set. Treatment-related adverse events (TRAEs) were observed in 96.7% of patients; diarrhea was the most common TRAE leading to dose reduction in 8.3% of patients (Table). No patients discontinued BAY 2927088 treatment because of diarrhea, and no cases of interstitial lung disease were reported. Investigator-assessed objective response rates were 59.3% (95% CI 47.8, 70.1; D) and 59.0% (95% CI 42.1, 74.4; F). Disease control rates (confirmed response or stable disease for ≥12 weeks) were 84.0% (95% CI 74.1, 91.2; D) and 84.6% (95% CI 69.5, 94.1; F). One patient in Cohort D achieved a complete response. Conclusions: BAY 2927088 demonstrated manageable safety in both cohorts, consistent with previous reports. Diarrhea was the most common TRAE, but it was manageable and did not lead to treatment discontinuation. Similar response rates were observed in patients with advanced HER2 -mutant NSCLC who were pretreated but naïve to HER2-targeted therapy and in those treated in the first-line setting. Clinical trial information: NCT05099172 . Cohort D(n=81) Cohort F(n=39) n (%) All grades Grade ≥3 All grades Grade ≥3 Any TRAE 78 (96.3) 31 (38.3) 38 (97.4) 8 (20.5) Most common TRAEs occurring in ≥20% of all patients Diarrhea 68 (84.0) 19 (23.5) 32 (82.1) 1 (2.6) Rash 40 (49.4) 0 22 (56.4) 0 Paronychia 20 (24.7) 0 7 (17.9) 0 Stomatitis 15 (18.5) 1 (1.2) 9 (23.1) 0 Most common TRAE leading to dose reduction Diarrhea 9 (11.1) 3 (3.7) 1 (2.6) 1 (2.6)